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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 66| Part 5| May 2010| Pages o1045-o1046
https://doi.org/10.1107/S1600536810012407

Ethenzamide–gentisic acid–acetic acid (2/1/1)

Srinivasulu Aitipamula,a* Pui Shan Chowa and Reginald B.H. Tana,b*

aInstitute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road, Jurong Island, 627833 Singapore, and bDepartment of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive, 117576 Singapore
*Correspondence e-mail: srinivasulu_aitipamula@ices.a-star.edu.sg, reginald_tan@ices.a-star.edu.sg

(Received 22 March 2010; accepted 1 April 2010; online 10 April 2010)

In the title co-crystal solvate, 2-ethoxy­benzamide–2,5-dihydroxy­benzoic acid–ethanoic acid (2/1/1), 2C9H11NO2·C7H6O4·C2H4O2, two nonsteroidal anti-inflammatory drugs, ethenzamide (systematic name: 2-ethoxy­benzamide) and gentisic acid (systematic name: 2,5-dihydroxy­benzoic acid), together with acetic acid (systematic name: ethanoic acid) form a four-component mol­ecular assembly held together by N—H⋯O and O—H⋯O hydrogen bonds. This assembly features two symmetry-independent mol­ecules of ethenzamide, forming supra­molecular acid–amide heterosynthons with gentisic acid and acetic acid. These heterosynthons involve quite strong O—H⋯O [O⋯O = 2.5446 (15) and 2.5327 (15) Å] and less strong N—H⋯O [N⋯O = 2.9550 (17) and 2.9542 (17) Å] hydrogen bonds. The overall crystal packing features several C—H⋯O and π–π stacking inter­actions [centroid–centroid distance = 3.7792 (11) Å].

Related literature

For information on three polymorphs of a 1:1 co-crystal involving ethenzamide and gentisic acid, see: Aitipamula et al. (2009a[Aitipamula, S., Chow, P. S. & Tan, R. B. H. (2009a). CrystEngComm, 11, 1823-1827.]). For other co-crystals of ethenzamide, see: Aitipamula et al. (2009b[Aitipamula, S., Chow, P. S. & Tan, R. B. H. (2009b). CrystEngComm, 11, 889-895.]); Moribe et al. (2004[Moribe, K., Tsuchiya, M., Tozuka, Y., Yamaguchi, K., Oguchi, T. & Yamamoto, K. (2004). Chem. Pharm. Bull. 52, 524-529.]). For related information on the drug activity of ethenzamide, see: Hirasawa et al. (1999[Hirasawa, N., Okamoto, H. & Danjo, K. (1999). Chem. Pharm. Bull. 47, 417-420.]). For the crystal structure of ethenzamide, see: Pagola & Stephens (2009[Pagola, S. & Stephens, P. W. (2009). Acta Cryst. C65, o583-o586.]). For related information on the drug activity of gentisic acid, see: Lorico et al. (1986[Lorico, A., Masturzo, P., Villa, S., Salmona, M., Semeraro, N. & Gaetano, G. D. (1986). Biochem. Pharmacol. 35, 2443-2445.]). For more information on the supra­molecular heterosynthons, see: Fleischman et al. (2003[Fleischman, S. G., Kuduva, S. S., McMahon, J. A., Moulton, B., Walsh, R. D. B., Rodríguez-Hornedo, N. & Zaworotko, M. J. (2003). Cryst. Growth Des. 3, 909-919.]). For reviews on pharmaceutical co-crystals, see: Schultheiss & Newman (2009[Schultheiss, N. & Newman, A. (2009). Cryst. Growth Des. 9, 2950-2967.]); Almarsson & Zaworotko (2004[Almarsson, Ö. & Zaworotko, M. J. (2004). Chem. Commun. pp. 1889-1896.]). For more information on the hydrogen bonding, see: Desiraju & Steiner (1999[Desiraju, G. R. & Steiner, T. (1999). The Weak Hydrogen Bond in Structural Chemistry and Biology, p. 13, IUCr Monographs on Crystallography, Vol. 9. Oxford University Press.]).

[Scheme 1]

Experimental

Crystal data

  • 2C9H11NO2·C7H6O4·C2H4O2

  • Mr = 544.55

  • Triclinic, [P \overline 1]

  • a = 8.8083 (18) Å

  • b = 8.8802 (18) Å

  • c = 19.880 (4) Å

  • α = 93.65 (3)°

  • β = 93.55 (3)°

  • γ = 119.45 (3)°

  • V = 1343.5 (6) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.10 mm−1

  • T = 110 K

  • 0.33 × 0.29 × 0.22 mm
Data collection

  • Rigaku Saturn CCD area-detector diffractometer

  • Absorption correction: multi-scan (Blessing, 1995[Blessing, R. H. (1995). Acta Cryst. A51, 33-38.]) Tmin = 0.967, Tmax = 0.978

  • 19296 measured reflections

  • 6594 independent reflections

  • 6074 reflections with I > 2σ(I)

  • Rint = 0.025
Refinement

  • R[F2 > 2σ(F2)] = 0.050

  • wR(F2) = 0.135

  • S = 1.11

  • 6594 reflections

  • 380 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.25 e Å−3

  • Δρmin = −0.23 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1⋯O2 0.926 (19) 1.941 (18) 2.6472 (19) 131.6 (14)
N1—H2⋯O5i 0.90 (2) 2.085 (18) 2.9550 (17) 163.0 (15)
N2—H7⋯O4 0.879 (18) 1.959 (17) 2.6536 (16) 135.0 (17)
N2—H10⋯O9ii 0.912 (18) 2.057 (17) 2.9542 (17) 167.4 (17)
O6—H11⋯O1iii 1.02 (2) 1.53 (2) 2.5327 (15) 167.0 (18)
O7—H16⋯O5 0.90 (2) 1.80 (2) 2.6183 (15) 149 (3)
O8—H19⋯O9iv 0.96 (2) 1.77 (2) 2.7231 (16) 173 (2)
O10—H20⋯O3v 0.99 (2) 1.56 (2) 2.5446 (15) 171 (2)
C8—H8A⋯O1vi 0.99 2.46 3.3768 (19) 154
C13—H13⋯O8vii 0.95 2.55 3.452 (2) 159
C14—H14⋯O10viii 0.95 2.53 3.348 (2) 145
Symmetry codes: (i) x+1, y+1, z+1; (ii) x-1, y, z; (iii) x-1, y-1, z-1; (iv) -x+2, -y+1, -z+1; (v) x+1, y, z; (vi) -x+1, -y+1, -z+2; (vii) x-1, y+1, z; (viii) -x, -y+1, -z+1.

Data collection: CrystalClear (Rigaku, 2008[Rigaku (2008). CrystalClear. Rigaku Corporation, Tokyo, Japan.]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: X-SEED (Barbour, 2001[Barbour, L. J. (2001). J. Supramol. Chem. 1, 189-191.]); software used to prepare material for publication: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536810012407/fb2192sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810012407/fb2192Isup2.hkl

checkCIF report


Comment top

Ethenzamide (2-ethoxybenzamide) belongs to a non-steroidal anti-inflammatory drug (NSAID) used mainly in combination with other ingredients for the treatment of mild to moderate pains (Hirasawa et al., 1999). The crystal structure of ethenzamide has been recently solved using the high-resolution powder X-ray diffraction (Pagola & Stephens, 2009). Gentisic acid (2,5-dihydroxybenzoic acid) is also a NSAID (Lorico et al., 1986).

Pharmaceutical cocrystals can be defined as molecular complexes formed between a neutral or ionic active pharmaceutical ingredient (API) and a pharmaceutically acceptable compound that is a solid under ambient conditions (Almarsson & Zaworotko, 2004). With our interest in pharmaceutical cocrystals and polymorphism, we recently reported three polymorphs of a 1:1 cocrystal involving ethenzamide and gentisic acid, and showed that the dissolution rates of the cocrystal polymorphs were improved twice when compared to that of the parent ethenzamide (Aitipamula et al., 2009a).

In attempt to prepare pure polymorphs of a cocrystal involving ethenzamide and gentisic acid, they were cocrystallized in 1:1 molar ratio from several organic solvents. Whereas all the crystallization batches resulted in reported 1:1 cocrystal polymorphs (Aitipamula et al., 2009a), crystallization from acetic acid yielded a solvate in which the ethenzamide, gentisic acid, and acetic acid were present in 2:1:1 molar ratio. We present here its crystal structure and analyze the hydrogen bonding.

The crystal structure contains two molecules of ethenzamide, one molecule of gentisic acid and one molecule of acetic acid in the asymmetric unit (Fig. 1). In the structure, gentisic acid and acetic acid molecules are engaged in the formation of acid-amide heterosynthons with symmetry independent molecules of ethenzamide involving quite strong O—H···O [O···O = 2.5446 (15) and 2.5327 (15) Å] and less strong N—H···O [N···O = 2.9550 (17) and 2.9542 (17) Å] hydrogen bonds (Table 1) (Desiraju & Steiner, 1999). The anti-N—H of the primary amide of ethenzamide and the 2-hydroxy group of gentisic acid form an intramolecular N—H···O [N···O = 2.6472 (19) and 2.6536 (16) Å] and O—H···O [O···O = 2.6183 (15)] hydrogen bonds, respectively (Table 1). Hydroxy atom of O8 of the gentisic acid acts as a hydrogen bond donor to atom O9 of the acetic acid at (2-x,1-y,1-z), and generates a four-component molecular assembly which involves two molecules of ethenzamide, one molecule each of gentisic acid and acetic acid (Fig. 2). It is worth mentioning that the solvent (acetic acid) molecule is an integral part of the four-component molecular assembly, which is bonded in the same way as the remaining constituents that participate in the heterosynthon formation. The four-component molecular assemblies are further stabilized in the crystal structure by various C—H···O interactions (Table 1) (Desiraju & Steiner, 1999), and by the π-π stacking interaction involving the phenyl rings of the molecules of ethenzamide and gentisic acid: Cg1···Cg2 (1-x, 1-y, 1-z) = 3.7792 (11) Å, where Cg1 and Cg2 denote the centroids of the rings C1—C6 and C19—C24 of ethenzamide and gentisic acid, respectively (Fig. 3).

In the light of the overwhelming interest in the development of pharmaceutical cocrystals for improving the physico-chemical properties of the APIs (Schultheiss & Newman, 2009), the title cocrystal solvate reported here presents some special features. First, it contains two APIs and thus can be considered as a multi-API cocrystal. Second, it contains the pharmaceutically acceptable acetic acid in the crystal structure. These two aspects make the title cocrystal solvate a potential solid form for development of a combination drug involving ethenzamide and gentisic acid.

Related literature top

For information on three polymorphs of a 1:1 co-crystal involving ethenzamide and gentisic acid, see: Aitipamula et al. (2009a). For other co-crystals of ethenzamide, see: Aitipamula et al. (2009b); Moribe et al. (2004). For related information on the drug activity of ethenzamide, see: Hirasawa et al. (1999). For the crystal structure of ethenzamide, see: Pagola & Stephens (2009). For related information on the drug activity of gentisic acid, see: Lorico et al. (1986). For more information on the supramolecular heterosynthons, see: Fleischman et al. (2003). For reviews on pharmaceutical co-crystals, see: Schultheiss & Newman (2009); Almarsson & Zaworotko (2004). For more information on the hydrogen bonding, see: Desiraju & Steiner (1999).

Experimental top

The title cocrystal solvate was obtained by slow evaporation of a glacial acetic acid (5 ml) solution of a 1:1 molar ratio of ethenzamide (100 mg, 0.605 mmol) and gentisic acid (93.3 mg, 0.605 mmol) at ambinent conditions. The block-shaped crystals, the dimensions of which were typically as those of the used sample for data collection, were obtained within 7 days.

Refinement top

Though all the H-atoms could be dinstinguished in the difference electron density map, the H-atoms bonded to C-atoms were included at the geometrically idealized positions and refined in riding-model approximation with C—H = 0.95 Å (aryl), 0.99 Å (methylene), and 0.98 Å (methyl). Uiso(H)aryl/methylene=1.2 Ueq(C) and Uiso(H)methyl=1.5 Ueq(C). The positional parameters of the H-atoms bonded to N and O were allowed to be refined freely while Uiso(H)amine=1.2 Ueq(N) and Uiso(H)hydroxyl=1.5 Ueq(O).

Structure description top

Ethenzamide (2-ethoxybenzamide) belongs to a non-steroidal anti-inflammatory drug (NSAID) used mainly in combination with other ingredients for the treatment of mild to moderate pains (Hirasawa et al., 1999). The crystal structure of ethenzamide has been recently solved using the high-resolution powder X-ray diffraction (Pagola & Stephens, 2009). Gentisic acid (2,5-dihydroxybenzoic acid) is also a NSAID (Lorico et al., 1986).

Pharmaceutical cocrystals can be defined as molecular complexes formed between a neutral or ionic active pharmaceutical ingredient (API) and a pharmaceutically acceptable compound that is a solid under ambient conditions (Almarsson & Zaworotko, 2004). With our interest in pharmaceutical cocrystals and polymorphism, we recently reported three polymorphs of a 1:1 cocrystal involving ethenzamide and gentisic acid, and showed that the dissolution rates of the cocrystal polymorphs were improved twice when compared to that of the parent ethenzamide (Aitipamula et al., 2009a).

In attempt to prepare pure polymorphs of a cocrystal involving ethenzamide and gentisic acid, they were cocrystallized in 1:1 molar ratio from several organic solvents. Whereas all the crystallization batches resulted in reported 1:1 cocrystal polymorphs (Aitipamula et al., 2009a), crystallization from acetic acid yielded a solvate in which the ethenzamide, gentisic acid, and acetic acid were present in 2:1:1 molar ratio. We present here its crystal structure and analyze the hydrogen bonding.

The crystal structure contains two molecules of ethenzamide, one molecule of gentisic acid and one molecule of acetic acid in the asymmetric unit (Fig. 1). In the structure, gentisic acid and acetic acid molecules are engaged in the formation of acid-amide heterosynthons with symmetry independent molecules of ethenzamide involving quite strong O—H···O [O···O = 2.5446 (15) and 2.5327 (15) Å] and less strong N—H···O [N···O = 2.9550 (17) and 2.9542 (17) Å] hydrogen bonds (Table 1) (Desiraju & Steiner, 1999). The anti-N—H of the primary amide of ethenzamide and the 2-hydroxy group of gentisic acid form an intramolecular N—H···O [N···O = 2.6472 (19) and 2.6536 (16) Å] and O—H···O [O···O = 2.6183 (15)] hydrogen bonds, respectively (Table 1). Hydroxy atom of O8 of the gentisic acid acts as a hydrogen bond donor to atom O9 of the acetic acid at (2-x,1-y,1-z), and generates a four-component molecular assembly which involves two molecules of ethenzamide, one molecule each of gentisic acid and acetic acid (Fig. 2). It is worth mentioning that the solvent (acetic acid) molecule is an integral part of the four-component molecular assembly, which is bonded in the same way as the remaining constituents that participate in the heterosynthon formation. The four-component molecular assemblies are further stabilized in the crystal structure by various C—H···O interactions (Table 1) (Desiraju & Steiner, 1999), and by the π-π stacking interaction involving the phenyl rings of the molecules of ethenzamide and gentisic acid: Cg1···Cg2 (1-x, 1-y, 1-z) = 3.7792 (11) Å, where Cg1 and Cg2 denote the centroids of the rings C1—C6 and C19—C24 of ethenzamide and gentisic acid, respectively (Fig. 3).

In the light of the overwhelming interest in the development of pharmaceutical cocrystals for improving the physico-chemical properties of the APIs (Schultheiss & Newman, 2009), the title cocrystal solvate reported here presents some special features. First, it contains two APIs and thus can be considered as a multi-API cocrystal. Second, it contains the pharmaceutically acceptable acetic acid in the crystal structure. These two aspects make the title cocrystal solvate a potential solid form for development of a combination drug involving ethenzamide and gentisic acid.

For information on three polymorphs of a 1:1 co-crystal involving ethenzamide and gentisic acid, see: Aitipamula et al. (2009a). For other co-crystals of ethenzamide, see: Aitipamula et al. (2009b); Moribe et al. (2004). For related information on the drug activity of ethenzamide, see: Hirasawa et al. (1999). For the crystal structure of ethenzamide, see: Pagola & Stephens (2009). For related information on the drug activity of gentisic acid, see: Lorico et al. (1986). For more information on the supramolecular heterosynthons, see: Fleischman et al. (2003). For reviews on pharmaceutical co-crystals, see: Schultheiss & Newman (2009); Almarsson & Zaworotko (2004). For more information on the hydrogen bonding, see: Desiraju & Steiner (1999).

Computing details top

Data collection: CrystalClear (Rigaku, 2008); cell refinement: CrystalClear (Rigaku, 2008); data reduction: CrystalClear (Rigaku, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The title molecules of ethenzamide, gentisic acid and aceitic acid with the atom labels and 50% probability displacement ellipsoids for non-H atoms.
[Figure 2] Fig. 2. The hydrogen bonded four-component molecular assembly in the crystal structure of the title cocrystal solvate. Atoms participating in the hydrogen bonding were labelled.
[Figure 3] Fig. 3. Section of the crystal structure, showing the π-π stacking interaction between the aromatic rings of the four-component molecular assemblies.
2-ethoxybenzamide—2,5-dihydroxybenzoic acid—ethanoic acid (2/1/1) top
Crystal data top
2C9H11NO2·C7H6O4·C2H4O2Z = 2
Mr = 544.55F(000) = 576
Triclinic, P1Dx = 1.346 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 8.8083 (18) ÅCell parameters from 3760 reflections
b = 8.8802 (18) Åθ = 2.1–31.0°
c = 19.880 (4) ŵ = 0.10 mm−1
α = 93.65 (3)°T = 110 K
β = 93.55 (3)°Block, yellow
γ = 119.45 (3)°0.33 × 0.29 × 0.22 mm
V = 1343.5 (6) Å3
Data collection top
Rigaku Saturn CCD area-detector
diffractometer		6594 independent reflections
Radiation source: fine-focus sealed tube6074 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.025
ω scansθmax = 28.3°, θmin = 2.1°
Absorption correction: multi-scan
(Blessing, 1995)		h = −11→11
Tmin = 0.967, Tmax = 0.978k = −11→9
19296 measured reflectionsl = −26→24
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.050H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.135 w = 1/[σ2(Fo2) + (0.0677P)2 + 0.2882P]
where P = (Fo2 + 2Fc2)/3
S = 1.11(Δ/σ)max = 0.001
6594 reflectionsΔρmax = 0.25 e Å−3
380 parametersΔρmin = −0.23 e Å−3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0054 (18)
Crystal data top
2C9H11NO2·C7H6O4·C2H4O2γ = 119.45 (3)°
Mr = 544.55V = 1343.5 (6) Å3
Triclinic, P1Z = 2
a = 8.8083 (18) ÅMo Kα radiation
b = 8.8802 (18) ŵ = 0.10 mm−1
c = 19.880 (4) ÅT = 110 K
α = 93.65 (3)°0.33 × 0.29 × 0.22 mm
β = 93.55 (3)°
Data collection top
Rigaku Saturn CCD area-detector
diffractometer		6594 independent reflections
Absorption correction: multi-scan
(Blessing, 1995)		6074 reflections with I > 2σ(I)
Tmin = 0.967, Tmax = 0.978Rint = 0.025
19296 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0500 restraints
wR(F2) = 0.135H atoms treated by a mixture of independent and constrained refinement
S = 1.11Δρmax = 0.25 e Å−3
6594 reflectionsΔρmin = −0.23 e Å−3
380 parameters
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O40.18598 (11)0.96579 (12)0.43017 (5)0.0280 (2)
O91.05478 (12)0.54627 (13)0.63748 (5)0.0319 (2)
O3−0.22283 (12)0.57234 (13)0.51754 (5)0.0324 (2)
O100.76432 (12)0.38996 (13)0.61300 (5)0.0316 (2)
H200.781 (2)0.464 (3)0.5756 (10)0.047*
N20.06949 (14)0.72419 (16)0.51542 (6)0.0281 (2)
H100.079 (2)0.668 (2)0.5509 (9)0.034*
H70.159 (2)0.811 (2)0.5000 (9)0.034*
C16−0.09157 (16)0.68847 (16)0.49396 (6)0.0249 (2)
C110.01615 (16)0.92217 (16)0.41021 (6)0.0251 (3)
C12−0.02542 (17)1.00581 (18)0.36157 (7)0.0295 (3)
H120.06541.09580.34090.035*
C180.49661 (17)1.13984 (19)0.43493 (7)0.0325 (3)
H18A0.50371.16040.48430.049*
H18B0.59321.24030.41800.049*
H18C0.50501.03560.42290.049*
C170.32440 (16)1.11405 (17)0.40346 (7)0.0285 (3)
H17A0.31501.21910.41490.034*
H17B0.31551.09250.35350.034*
C10−0.11871 (16)0.78677 (16)0.44080 (6)0.0246 (2)
C15−0.29227 (16)0.74279 (17)0.42099 (7)0.0277 (3)
H15−0.38440.65260.44110.033*
C13−0.19922 (18)0.95831 (18)0.34313 (7)0.0308 (3)
H13−0.22641.01620.30990.037*
C260.91047 (17)0.43317 (17)0.65051 (7)0.0283 (3)
C14−0.33339 (17)0.82690 (18)0.37295 (7)0.0308 (3)
H14−0.45210.79510.36050.037*
C270.8867 (2)0.3342 (2)0.71097 (8)0.0371 (3)
H27A0.98740.31680.71990.056*
H27B0.77910.22090.70200.056*
H27C0.87800.40010.75050.056*
O10.91975 (12)0.71644 (12)1.01611 (5)0.0296 (2)
O20.45825 (12)0.67508 (13)0.93005 (5)0.0298 (2)
C10.66698 (16)0.57974 (16)0.93614 (6)0.0247 (2)
N10.75912 (17)0.84922 (16)1.00868 (6)0.0322 (3)
H10.656 (2)0.845 (2)0.9926 (9)0.039*
H20.829 (2)0.926 (2)1.0438 (9)0.039*
C70.78960 (16)0.72148 (16)0.98983 (6)0.0254 (2)
C20.50360 (17)0.55485 (16)0.90874 (6)0.0262 (3)
C60.71780 (18)0.46025 (17)0.91414 (7)0.0291 (3)
H60.82780.47600.93210.035*
C80.28786 (17)0.65018 (19)0.90704 (7)0.0316 (3)
H8A0.19400.54340.92280.038*
H8B0.27100.63940.85690.038*
C90.2832 (2)0.8079 (2)0.93678 (8)0.0388 (3)
H9A0.30250.81810.98630.058*
H9B0.16870.79610.92320.058*
H9C0.37550.91230.92010.058*
C40.44999 (19)0.29481 (18)0.84136 (7)0.0344 (3)
H40.37590.19740.80930.041*
C30.39524 (18)0.41077 (18)0.86209 (7)0.0314 (3)
H30.28390.39210.84450.038*
C50.61151 (19)0.31929 (18)0.86680 (7)0.0330 (3)
H50.64890.24020.85190.040*
O80.70122 (13)0.23351 (13)0.25999 (5)0.0327 (2)
H190.784 (3)0.317 (3)0.2955 (10)0.049*
O60.13707 (13)−0.09895 (13)0.11728 (5)0.0319 (2)
H110.039 (3)−0.166 (3)0.0787 (10)0.048*
O5−0.01505 (12)0.03810 (13)0.13600 (5)0.0327 (2)
O70.10781 (13)0.29851 (13)0.23160 (5)0.0325 (2)
H160.033 (3)0.217 (3)0.1981 (10)0.049*
C240.41450 (17)0.13298 (16)0.20904 (6)0.0254 (2)
H240.42100.04170.18420.030*
C220.54594 (17)0.38590 (17)0.29022 (6)0.0285 (3)
H220.64320.46910.32070.034*
C230.55542 (16)0.25175 (17)0.25389 (6)0.0264 (3)
C190.26205 (16)0.14500 (16)0.19962 (6)0.0248 (2)
C250.11617 (17)0.02315 (16)0.14875 (6)0.0262 (3)
C210.39528 (17)0.39826 (17)0.28208 (7)0.0285 (3)
H210.38940.48900.30760.034*
C200.25202 (17)0.27906 (17)0.23681 (6)0.0263 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O40.0206 (4)0.0310 (5)0.0326 (5)0.0122 (4)0.0044 (3)0.0081 (4)
O90.0255 (4)0.0373 (5)0.0296 (5)0.0130 (4)0.0020 (3)0.0044 (4)
O30.0221 (4)0.0334 (5)0.0383 (5)0.0106 (4)0.0038 (4)0.0089 (4)
O100.0241 (4)0.0338 (5)0.0340 (5)0.0119 (4)0.0045 (4)0.0054 (4)
N20.0215 (5)0.0322 (6)0.0288 (5)0.0116 (4)0.0025 (4)0.0071 (4)
C160.0222 (5)0.0254 (6)0.0258 (6)0.0112 (5)0.0028 (4)−0.0010 (4)
C110.0230 (5)0.0271 (6)0.0257 (6)0.0136 (5)0.0007 (4)−0.0018 (5)
C120.0292 (6)0.0305 (6)0.0301 (6)0.0160 (5)0.0026 (5)0.0035 (5)
C180.0246 (6)0.0338 (7)0.0383 (7)0.0130 (5)0.0055 (5)0.0097 (6)
C170.0243 (6)0.0285 (6)0.0314 (6)0.0115 (5)0.0059 (5)0.0068 (5)
C100.0234 (6)0.0246 (6)0.0251 (6)0.0121 (5)0.0010 (4)−0.0025 (4)
C150.0234 (6)0.0258 (6)0.0308 (6)0.0111 (5)−0.0010 (5)−0.0037 (5)
C130.0327 (7)0.0301 (7)0.0317 (6)0.0185 (5)−0.0046 (5)−0.0006 (5)
C260.0293 (6)0.0302 (6)0.0275 (6)0.0166 (5)0.0049 (5)0.0002 (5)
C140.0254 (6)0.0301 (7)0.0359 (7)0.0149 (5)−0.0050 (5)−0.0040 (5)
C270.0446 (8)0.0372 (8)0.0330 (7)0.0220 (6)0.0083 (6)0.0079 (6)
O10.0282 (4)0.0290 (5)0.0326 (5)0.0159 (4)−0.0005 (4)−0.0008 (4)
O20.0302 (5)0.0331 (5)0.0305 (5)0.0195 (4)0.0020 (4)0.0017 (4)
C10.0276 (6)0.0228 (6)0.0231 (6)0.0117 (5)0.0045 (4)0.0048 (4)
N10.0356 (6)0.0299 (6)0.0338 (6)0.0201 (5)−0.0035 (5)−0.0042 (5)
C70.0280 (6)0.0238 (6)0.0253 (6)0.0130 (5)0.0050 (4)0.0054 (4)
C20.0299 (6)0.0275 (6)0.0235 (6)0.0154 (5)0.0062 (5)0.0060 (5)
C60.0309 (6)0.0281 (6)0.0306 (6)0.0162 (5)0.0053 (5)0.0039 (5)
C80.0275 (6)0.0372 (7)0.0342 (7)0.0186 (6)0.0047 (5)0.0091 (5)
C90.0370 (7)0.0420 (8)0.0474 (8)0.0261 (7)0.0089 (6)0.0101 (6)
C40.0375 (7)0.0292 (7)0.0298 (7)0.0123 (6)0.0017 (5)−0.0008 (5)
C30.0299 (6)0.0316 (7)0.0290 (6)0.0126 (5)0.0018 (5)0.0025 (5)
C50.0391 (7)0.0288 (7)0.0332 (7)0.0188 (6)0.0052 (5)−0.0001 (5)
O80.0291 (5)0.0363 (5)0.0357 (5)0.0198 (4)−0.0039 (4)−0.0006 (4)
O60.0344 (5)0.0295 (5)0.0336 (5)0.0193 (4)−0.0058 (4)−0.0050 (4)
O50.0278 (5)0.0350 (5)0.0357 (5)0.0176 (4)−0.0032 (4)−0.0034 (4)
O70.0290 (5)0.0329 (5)0.0383 (5)0.0185 (4)0.0006 (4)−0.0026 (4)
C240.0287 (6)0.0240 (6)0.0249 (6)0.0141 (5)0.0025 (4)0.0037 (4)
C220.0297 (6)0.0260 (6)0.0257 (6)0.0110 (5)0.0007 (5)0.0016 (5)
C230.0260 (6)0.0278 (6)0.0266 (6)0.0142 (5)0.0021 (4)0.0054 (5)
C190.0255 (6)0.0235 (6)0.0243 (6)0.0113 (5)0.0019 (4)0.0037 (4)
C250.0271 (6)0.0255 (6)0.0266 (6)0.0135 (5)0.0029 (4)0.0040 (5)
C210.0314 (6)0.0254 (6)0.0287 (6)0.0142 (5)0.0034 (5)0.0012 (5)
C200.0269 (6)0.0264 (6)0.0270 (6)0.0138 (5)0.0045 (4)0.0051 (5)
Geometric parameters (Å, º) top
O4—C111.3720 (15)C1—C71.4965 (19)
O4—C171.4466 (16)N1—C71.3256 (17)
O9—C261.2289 (17)N1—H10.930 (19)
O3—C161.2555 (16)N1—H20.90 (2)
O10—C261.3112 (17)C2—C31.395 (2)
O10—H200.99 (2)C6—C51.385 (2)
N2—C161.3269 (16)C6—H60.9500
N2—H100.913 (18)C8—C91.506 (2)
N2—H70.879 (18)C8—H8A0.9900
C16—C101.4924 (19)C8—H8B0.9900
C11—C121.3913 (19)C9—H9A0.9800
C11—C101.4159 (18)C9—H9B0.9800
C12—C131.3899 (18)C9—H9C0.9800
C12—H120.9500C4—C51.386 (2)
C18—C171.5058 (18)C4—C31.386 (2)
C18—H18A0.9800C4—H40.9500
C18—H18B0.9800C3—H30.9500
C18—H18C0.9800C5—H50.9500
C17—H17A0.9900O8—C231.3705 (16)
C17—H17B0.9900O8—H190.96 (2)
C10—C151.4012 (17)O6—C251.3134 (16)
C15—C141.384 (2)O6—H111.02 (2)
C15—H150.9500O5—C251.2397 (16)
C13—C141.389 (2)O7—C201.3622 (16)
C13—H130.9500O7—H160.90 (2)
C26—C271.499 (2)C24—C231.3798 (19)
C14—H140.9500C24—C191.4007 (18)
C27—H27A0.9800C24—H240.9500
C27—H27B0.9800C22—C211.3849 (19)
C27—H27C0.9800C22—C231.3941 (19)
O1—C71.2523 (16)C22—H220.9500
O2—C21.3644 (16)C19—C201.4040 (18)
O2—C81.4444 (16)C19—C251.4756 (19)
C1—C61.3963 (18)C21—C201.3955 (19)
C1—C21.4112 (18)C21—H210.9500
C11—O4—C17117.67 (10)O1—C7—N1121.31 (12)
C26—O10—H20113.5 (11)O1—C7—C1118.85 (12)
C16—N2—H10116.3 (11)N1—C7—C1119.85 (12)
C16—N2—H7119.0 (11)O2—C2—C3122.70 (12)
H10—N2—H7123.8 (16)O2—C2—C1117.45 (11)
O3—C16—N2121.07 (12)C3—C2—C1119.85 (12)
O3—C16—C10119.00 (11)C5—C6—C1121.49 (13)
N2—C16—C10119.93 (12)C5—C6—H6119.3
O4—C11—C12122.18 (12)C1—C6—H6119.3
O4—C11—C10117.69 (11)O2—C8—C9106.37 (12)
C12—C11—C10120.13 (12)O2—C8—H8A110.5
C13—C12—C11120.32 (13)C9—C8—H8A110.5
C13—C12—H12119.8O2—C8—H8B110.5
C11—C12—H12119.8C9—C8—H8B110.5
C17—C18—H18A109.5H8A—C8—H8B108.6
C17—C18—H18B109.5C8—C9—H9A109.5
H18A—C18—H18B109.5C8—C9—H9B109.5
C17—C18—H18C109.5H9A—C9—H9B109.5
H18A—C18—H18C109.5C8—C9—H9C109.5
H18B—C18—H18C109.5H9A—C9—H9C109.5
O4—C17—C18107.57 (11)H9B—C9—H9C109.5
O4—C17—H17A110.2C5—C4—C3120.78 (13)
C18—C17—H17A110.2C5—C4—H4119.6
O4—C17—H17B110.2C3—C4—H4119.6
C18—C17—H17B110.2C4—C3—C2120.05 (13)
H17A—C17—H17B108.5C4—C3—H3120.0
C15—C10—C11117.89 (12)C2—C3—H3120.0
C15—C10—C16116.73 (12)C6—C5—C4119.29 (13)
C11—C10—C16125.37 (11)C6—C5—H5120.4
C14—C15—C10121.93 (13)C4—C5—H5120.4
C14—C15—H15119.0C23—O8—H19109.3 (12)
C10—C15—H15119.0C25—O6—H11110.3 (11)
C14—C13—C12120.47 (13)C20—O7—H16105.4 (13)
C14—C13—H13119.8C23—C24—C19120.98 (12)
C12—C13—H13119.8C23—C24—H24119.5
O9—C26—O10122.84 (13)C19—C24—H24119.5
O9—C26—C27122.78 (13)C21—C22—C23120.24 (12)
O10—C26—C27114.38 (12)C21—C22—H22119.9
C15—C14—C13119.25 (12)C23—C22—H22119.9
C15—C14—H14120.4O8—C23—C24117.91 (12)
C13—C14—H14120.4O8—C23—C22122.62 (12)
C26—C27—H27A109.5C24—C23—C22119.46 (12)
C26—C27—H27B109.5C24—C19—C20119.47 (12)
H27A—C27—H27B109.5C24—C19—C25120.45 (12)
C26—C27—H27C109.5C20—C19—C25120.02 (12)
H27A—C27—H27C109.5O5—C25—O6122.74 (12)
H27B—C27—H27C109.5O5—C25—C19121.85 (12)
C2—O2—C8119.79 (11)O6—C25—C19115.40 (11)
C6—C1—C2118.51 (12)C22—C21—C20120.82 (12)
C6—C1—C7116.30 (12)C22—C21—H21119.6
C2—C1—C7125.14 (12)C20—C21—H21119.6
C7—N1—H1120.7 (11)O7—C20—C21117.69 (12)
C7—N1—H2117.4 (12)O7—C20—C19123.28 (12)
H1—N1—H2120.6 (16)C21—C20—C19119.02 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O20.926 (19)1.941 (18)2.6472 (19)131.6 (14)
N1—H2···O5i0.90 (2)2.085 (18)2.9550 (17)163.0 (15)
N2—H7···O40.879 (18)1.959 (17)2.6536 (16)135.0 (17)
N2—H10···O9ii0.912 (18)2.057 (17)2.9542 (17)167.4 (17)
O6—H11···O1iii1.02 (2)1.53 (2)2.5327 (15)167.0 (18)
O7—H16···O50.90 (2)1.80 (2)2.6183 (15)149 (3)
O8—H19···O9iv0.96 (2)1.77 (2)2.7231 (16)173 (2)
O10—H20···O3v0.99 (2)1.56 (2)2.5446 (15)171 (2)
C8—H8A···O1vi0.992.463.3768 (19)154
C13—H13···O8vii0.952.553.452 (2)159
C14—H14···O10viii0.952.533.348 (2)145
Symmetry codes: (i) x+1, y+1, z+1; (ii) x−1, y, z; (iii) x−1, y−1, z−1; (iv) −x+2, −y+1, −z+1; (v) x+1, y, z; (vi) −x+1, −y+1, −z+2; (vii) x−1, y+1, z; (viii) −x, −y+1, −z+1.

Experimental details

Crystal data
Chemical formula2C9H11NO2·C7H6O4·C2H4O2
Mr544.55
Crystal system, space groupTriclinic, P1
Temperature (K)110
a, b, c (Å)8.8083 (18), 8.8802 (18), 19.880 (4)
α, β, γ (°)93.65 (3), 93.55 (3), 119.45 (3)
V (Å3)1343.5 (6)
Z2
Radiation typeMo Kα
µ (mm−1)0.10
Crystal size (mm)0.33 × 0.29 × 0.22
Data collection
DiffractometerRigaku Saturn CCD area-detector
Absorption correctionMulti-scan
(Blessing, 1995)
Tmin, Tmax0.967, 0.978
No. of measured, independent and
observed [I > 2σ(I)] reflections		19296, 6594, 6074
Rint0.025
(sin θ/λ)max (Å−1)0.667
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.050, 0.135, 1.11
No. of reflections6594
No. of parameters380
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)0.25, −0.23

Computer programs: CrystalClear (Rigaku, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), X-SEED (Barbour, 2001), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O20.926 (19)1.941 (18)2.6472 (19)131.6 (14)
N1—H2···O5i0.90 (2)2.085 (18)2.9550 (17)163.0 (15)
N2—H7···O40.879 (18)1.959 (17)2.6536 (16)135.0 (17)
N2—H10···O9ii0.912 (18)2.057 (17)2.9542 (17)167.4 (17)
O6—H11···O1iii1.02 (2)1.53 (2)2.5327 (15)167.0 (18)
O7—H16···O50.90 (2)1.80 (2)2.6183 (15)149 (3)
O8—H19···O9iv0.96 (2)1.77 (2)2.7231 (16)173 (2)
O10—H20···O3v0.99 (2)1.56 (2)2.5446 (15)171 (2)
C8—H8A···O1vi0.992.463.3768 (19)154
C13—H13···O8vii0.952.553.452 (2)159
C14—H14···O10viii0.952.533.348 (2)145
Symmetry codes: (i) x+1, y+1, z+1; (ii) x−1, y, z; (iii) x−1, y−1, z−1; (iv) −x+2, −y+1, −z+1; (v) x+1, y, z; (vi) −x+1, −y+1, −z+2; (vii) x−1, y+1, z; (viii) −x, −y+1, −z+1.
 

Acknowledgements

This work was supported by the Institute of Chemical and Engineering Sciences of A*STAR (Agency for Science, Technology and Research), Singapore.

References

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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 66| Part 5| May 2010| Pages o1045-o1046
https://doi.org/10.1107/S1600536810012407
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