4-[3,5-Bis(2-hy­droxy­phen­yl)-1H-1,2,4-triazol-1-yl]benzoic acid dimethyl­formamide monosolvate

Fun, H.-K.; Chantrapromma, S.; Dayananda, A.S.; Yathirajan, H.S.; Thomas, S.

doi:10.1107/S1600536812005806

organic compounds

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ISSN: 2056-9890

Volume 68| Part 3| March 2012| Pages o792-o793

doi:10.1107/S1600536812005806

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4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid dimethylformamide monosolvate

Hoong-Kun Fun,^a ^*‡ Suchada Chantrapromma,^b § A. S. Dayananda,^c H. S. Yathirajan ^c and Saji Thomas ^d

^aX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia, ^bCrystal Materials Research Unit, Department of Chemistry, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand, ^cDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India, and ^dJubilant Life Sciences Ltd, R&D Centre, C-26, Sector 59, Noida 201 301, India
^*Correspondence e-mail: hkfun@usm.my

(Received 23 January 2012; accepted 9 February 2012; online 24 February 2012)

In the molecule of deferasirox dimethylformamide solvate, C₂₁H₁₅N₃O₄·C₃H₇NO, the central 1,2,4-triazole ring is tilted with respect to the benzoic acid and one of the 2-hydroxyphenyl units but coplanar with the other 2-hydroxyphenyl group, as indicated by the dihedral angles of 33.69 (9), 72.57 (8) and 5.18 (9)°, respectively. Intramolecular O—H⋯N hydrogen bonds generate an S(6) ring motif. In the crystal, deferasirox molecules are linked by O—H⋯N hydrogen bonds and weak C—H⋯O interactions into chains along the c axis. The dimethylformamide solvent molecules are located between the deferasirox chains and are linked to the deferasirox molecules by O—H⋯O hydrogen bonds and weak C—H⋯O interactions.

Related literature

For bond-length data, see: Allen et al. (1987 ). For graph-set notation, see Bernstein et al. (1995 ). For background to, and applications of, deferasirox, see: Choudhry & Naithani (2007 ); Lalitha Manasa et al. (2011 ); Nick et al. (2003 ); Yang et al. (2007 ). For related structures, see: Ishak et al. (2011 ); Rajnikant et al. (2006 ); Yathirajan et al. (2006 , 2007 ). For the stability of the temperature controller, see Cosier & Glazer (1986 ).

Experimental

Crystal data

C₂₁H₁₅N₃O₄·C₃H₇NO
M_r = 446.46
Monoclinic, P 2₁ /c
a = 8.8172 (8) Å
b = 32.669 (3) Å
c = 7.6900 (7) Å
β = 94.901 (2)°
V = 2207.0 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.32 × 0.25 × 0.11 mm

Data collection

Bruker APEX DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ) T_min = 0.970, T_max = 0.989
18347 measured reflections
6379 independent reflections
4384 reflections with I > 2σ(I)
R_int = 0.038

Refinement

R[F² > 2σ(F²)] = 0.058
wR(F²) = 0.144
S = 1.04
6379 reflections
303 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.59 e Å⁻³
Δρ_min = −0.56 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H1O2⋯O5ⁱ	0.90	1.68	2.583 (3)	173
O3—H1O3⋯N2	0.91 (3)	1.83 (3)	2.645 (2)	148 (2)
O4—H1O4⋯N3ⁱⁱ	1.00	1.79	2.7548 (19)	161
C2—H2A⋯O2ⁱⁱⁱ	0.95	2.51	3.340 (3)	146
C12—H12A⋯O1^iv	0.95	2.59	3.436 (2)	149
C15—H15A⋯O4^v	0.95	2.48	3.385 (2)	160
C22—H22A⋯O1^vi	0.95	2.42	3.085 (3)	127
Symmetry codes: (i) x, y, z+1; (ii) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (iii) -x+1, -y, -z+2; (iv) x+1, y, z-1; (v) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (vi) x, y, z-1.

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536812005806/ez2281sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812005806/ez2281Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812005806/ez2281Isup3.cml

checkCIF report

Comment top

The main use of deferasirox (IUPAC name: [4-[3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid) is to reduce chronic iron overload in patients who are receiving long-term blood transfusions. Reviews on the use of deferasirox (Yang et al., 2007) and its structure-activity properties (Nick et al., 2003) have been published. The current status of iron overload and chelation with deferasirox has been described (Choudhry & Naithani, 2007). Novel spectrophotometric methods for the determination of deferasirox have been reported (Lalitha Manasa et al., 2011). The crystal structures of 1-2-4-triazole derivatives have been reported (Ishak et al., 2011; Rajnikant et al., 2006; Yathirajan et al., 2006; 2007). In view of the importance of deferasirox, the crystal structure of the title compound (I) is reported.

The asymmetric unit of (I), C₂₁H₁₅N₃O₄.C₃H₇NO, comprises the deferasirox molecule and one dimethylformamide solvent molecule. In the deferasirox molecule, the central 1,2,4-triazole ring makes the dihedral angles of 33.69 (9), 5.18 (9) and 72.57 (8)° with the C1–C6, C10–C15 and C16–C21 benzene rings respectively, indicating that the 1,2,4-triazole ring is tilted with respect to the benzoic acid (C1–C6 ring) and one of the 2-hydroxyphenyl (C10–C15 ring) moieties, whereas it is co-planar with the other 2-hydroxyphenyl (C16–C21 ring) moiety.

An intramolecular O3—H1O3···N2 hydrogen bond generates an S(6) ring motif (Bernstein et al., 1995) which helps to stabilize the planarity of the 1,2,4-triazole and 2-hydroxyphenyl moiety (C10–C15/O3), with the r.m.s = 0.342 (2) Å for the twelve non-H atoms (C8–C15/N1–N3/O3). The dihedral angle between the two 2-hydroxyphenyl rings is 76.56 (8)°, whereas the C1–C6 ring of the benzoic acid makes the dihedral angles of 38.04 (9) and 67.34 (8)° with the C10–C15 and C16–C21 rings, respectively. Bond distances of (I) are in normal range (Allen et al., 1987) and comparable with the related structures (Ishak et al., (2011); Rajnikant et al., (2006) and Yathirajan et al., (2006; 2007).

In the crystal packing (Fig. 2), the molecules of deferasirox are linked by intermolecular O—H···N hydrogen bonds and weak C—H···O interactions (Table 1) into chains along the c axis. The dimethylformamide solvent molecules are located at the interstitials of the deferasirox chains and linked to the deferasirox molecules by O—H···O hydrogen bonds and weak C—H···O interactions (Fig. 2 and Table 1).

Related literature top

For bond-length data, see: Allen et al. (1987). For related literature on hydrogen-bond motifs, see Bernstein et al. (1995). For background to, and applications of, deferasirox, see: Choudhry & Naithani (2007); Lalitha Manasa et al. (2011); Nick et al. (2003); Yang et al. (2007). For related structures, see: Ishak et al. (2011); Rajnikant et al. (2006); Yathirajan et al. (2006, 2007). For the stability of the temperature controller, see Cosier & Glazer (1986).

Experimental top

The title compound was obtained as a gift sample from Jubilant Life Sciences, Noida, India. Colorless block-shaped single crystals of the title compound suitable for X-ray structure determination were recrystalized from toluene/dimethylformamide (1:1 v/v) by slow evaporation of the solvent at room temperature after several days. Mp. 539–540 K.

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top

	Fig. 1. The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme. The intramolecular O—H···N hydrogen bond is shown as a dashed line.
	Fig. 2. The crystal packing of the title compound viewed along the a axis. For the sake of clarity, only H atoms involved in hydrogen bonds are shown. Hydrogen bonds are drawn as dashed lines.

4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid dimethylformamide monosolvate top

Crystal data top

C₂₁H₁₅N₃O₄·C₃H₇NO	F(000) = 936
M_r = 446.46	D_x = 1.344 Mg m⁻³
Monoclinic, P2₁/c	Melting point = 539–540 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 8.8172 (8) Å	Cell parameters from 6379 reflections
b = 32.669 (3) Å	θ = 2.3–30.0°
c = 7.6900 (7) Å	µ = 0.10 mm⁻¹
β = 94.901 (2)°	T = 100 K
V = 2207.0 (3) Å³	Block, colorless
Z = 4	0.32 × 0.25 × 0.11 mm

Data collection top

Bruker APEX DUO CCD area-detector diffractometer	6379 independent reflections
Radiation source: sealed tube	4384 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.038
ϕ and ω scans	θ_max = 30.0°, θ_min = 2.3°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −12→11
T_min = 0.970, T_max = 0.989	k = −44→45
18347 measured reflections	l = −10→10

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.058	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.144	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ²(F_o²) + (0.0461P)² + 1.5844P] where P = (F_o² + 2F_c²)/3
6379 reflections	(Δ/σ)_max = 0.001
303 parameters	Δρ_max = 0.59 e Å⁻³
0 restraints	Δρ_min = −0.56 e Å⁻³

Crystal data top

C₂₁H₁₅N₃O₄·C₃H₇NO	V = 2207.0 (3) Å³
M_r = 446.46	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 8.8172 (8) Å	µ = 0.10 mm⁻¹
b = 32.669 (3) Å	T = 100 K
c = 7.6900 (7) Å	0.32 × 0.25 × 0.11 mm
β = 94.901 (2)°

Data collection top

Bruker APEX DUO CCD area-detector diffractometer	6379 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2009)	4384 reflections with I > 2σ(I)
T_min = 0.970, T_max = 0.989	R_int = 0.038
18347 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.058	0 restraints
wR(F²) = 0.144	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	Δρ_max = 0.59 e Å⁻³
6379 reflections	Δρ_min = −0.56 e Å⁻³
303 parameters

Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.

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 > 2sigma(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

	x	y	z	U_iso*/U_eq
O1	0.33110 (15)	0.08811 (4)	1.31456 (16)	0.0238 (3)
O2	0.3878 (3)	0.02777 (5)	1.2036 (2)	0.0742 (8)
H1O2	0.3513	0.0199	1.3047	0.111*
O3	0.90883 (15)	0.10202 (5)	0.38917 (18)	0.0311 (3)
H1O3	0.830 (3)	0.1058 (8)	0.456 (3)	0.047*
O4	0.46909 (15)	0.25263 (4)	0.60966 (19)	0.0306 (3)
H1O4	0.4693	0.2783	0.6808	0.046*
O5	0.2916 (3)	−0.00057 (5)	0.4879 (2)	0.0792 (8)
N1	0.52636 (15)	0.14408 (4)	0.56919 (18)	0.0167 (3)
N2	0.64907 (15)	0.13126 (5)	0.48553 (18)	0.0198 (3)
N3	0.52841 (16)	0.18321 (4)	0.33783 (18)	0.0184 (3)
N4	0.1441 (3)	0.01691 (6)	0.7044 (2)	0.0470 (5)
C1	0.4152 (2)	0.08640 (5)	1.0291 (2)	0.0226 (4)
C2	0.4791 (3)	0.06402 (6)	0.8993 (3)	0.0371 (5)
H2A	0.4978	0.0356	0.9155	0.045*
C3	0.5156 (2)	0.08293 (6)	0.7465 (2)	0.0302 (4)
H3A	0.5586	0.0676	0.6579	0.036*
C4	0.48836 (18)	0.12443 (5)	0.7255 (2)	0.0175 (3)
C5	0.42428 (19)	0.14715 (5)	0.8531 (2)	0.0188 (3)
H5A	0.4061	0.1756	0.8371	0.023*
C6	0.38716 (18)	0.12784 (5)	1.0040 (2)	0.0176 (3)
H6A	0.3420	0.1431	1.0912	0.021*
C7	0.3750 (2)	0.06792 (5)	1.1966 (2)	0.0261 (4)
C8	0.45577 (18)	0.17495 (5)	0.4780 (2)	0.0162 (3)
C9	0.64624 (18)	0.15571 (5)	0.3471 (2)	0.0174 (3)
C10	0.75991 (18)	0.15289 (5)	0.2187 (2)	0.0194 (3)
C11	0.88427 (19)	0.12628 (6)	0.2452 (2)	0.0234 (4)
C12	0.9916 (2)	0.12447 (7)	0.1219 (3)	0.0301 (4)
H12A	1.0766	0.1066	0.1403	0.036*
C13	0.9752 (2)	0.14846 (7)	−0.0266 (3)	0.0300 (4)
H13A	1.0485	0.1469	−0.1099	0.036*
C14	0.8524 (2)	0.17481 (6)	−0.0546 (2)	0.0274 (4)
H14A	0.8409	0.1911	−0.1571	0.033*
C15	0.7463 (2)	0.17722 (6)	0.0682 (2)	0.0228 (4)
H15A	0.6631	0.1956	0.0499	0.027*
C16	0.31623 (19)	0.19581 (5)	0.5244 (2)	0.0178 (3)
C17	0.3273 (2)	0.23590 (5)	0.5890 (2)	0.0210 (3)
C18	0.1957 (2)	0.25621 (6)	0.6290 (2)	0.0247 (4)
H18A	0.2015	0.2836	0.6701	0.030*
C19	0.0568 (2)	0.23642 (6)	0.6089 (2)	0.0253 (4)
H19A	−0.0323	0.2503	0.6376	0.030*
C20	0.0455 (2)	0.19649 (6)	0.5472 (2)	0.0240 (4)
H20A	−0.0506	0.1832	0.5341	0.029*
C21	0.17560 (19)	0.17613 (5)	0.5049 (2)	0.0203 (3)
H21A	0.1687	0.1488	0.4627	0.024*
C22	0.2029 (3)	0.02297 (7)	0.5528 (3)	0.0466 (6)
H22A	0.1744	0.0472	0.4900	0.056*
C23	0.0407 (3)	0.04676 (10)	0.7700 (3)	0.0563 (7)
H23A	0.0277	0.0697	0.6882	0.085*
H23B	0.0829	0.0568	0.8841	0.085*
H23C	−0.0583	0.0339	0.7819	0.085*
C24	0.1866 (6)	−0.01805 (8)	0.8146 (4)	0.0949 (15)
H24A	0.2634	−0.0343	0.7608	0.142*
H24B	0.0965	−0.0350	0.8277	0.142*
H24C	0.2284	−0.0085	0.9295	0.142*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0325 (7)	0.0215 (6)	0.0185 (6)	0.0024 (5)	0.0092 (5)	−0.0005 (5)
O2	0.173 (2)	0.0205 (8)	0.0388 (9)	0.0265 (11)	0.0645 (12)	0.0114 (7)
O3	0.0238 (6)	0.0473 (9)	0.0231 (7)	0.0112 (6)	0.0075 (5)	0.0051 (6)
O4	0.0321 (7)	0.0239 (7)	0.0376 (8)	−0.0077 (6)	0.0132 (6)	−0.0149 (6)
O5	0.182 (2)	0.0248 (8)	0.0402 (10)	0.0076 (12)	0.0640 (13)	0.0047 (7)
N1	0.0168 (6)	0.0176 (7)	0.0166 (7)	0.0009 (5)	0.0056 (5)	0.0007 (5)
N2	0.0170 (6)	0.0253 (8)	0.0178 (7)	0.0018 (6)	0.0064 (5)	0.0001 (6)
N3	0.0219 (7)	0.0173 (7)	0.0167 (7)	−0.0017 (5)	0.0052 (5)	−0.0009 (5)
N4	0.0819 (15)	0.0402 (11)	0.0216 (9)	−0.0273 (11)	0.0198 (10)	−0.0057 (8)
C1	0.0319 (9)	0.0205 (8)	0.0167 (8)	0.0051 (7)	0.0089 (7)	0.0024 (6)
C2	0.0672 (15)	0.0212 (9)	0.0263 (10)	0.0179 (10)	0.0233 (10)	0.0075 (8)
C3	0.0477 (12)	0.0240 (9)	0.0214 (9)	0.0136 (8)	0.0182 (8)	0.0032 (7)
C4	0.0181 (7)	0.0200 (8)	0.0149 (7)	0.0009 (6)	0.0033 (6)	0.0021 (6)
C5	0.0235 (8)	0.0163 (8)	0.0168 (8)	0.0009 (6)	0.0032 (6)	−0.0006 (6)
C6	0.0198 (7)	0.0179 (8)	0.0154 (7)	0.0006 (6)	0.0037 (6)	−0.0020 (6)
C7	0.0399 (10)	0.0202 (9)	0.0197 (8)	0.0056 (8)	0.0113 (8)	0.0036 (7)
C8	0.0186 (7)	0.0147 (7)	0.0158 (7)	−0.0021 (6)	0.0037 (6)	−0.0018 (6)
C9	0.0153 (7)	0.0202 (8)	0.0170 (8)	−0.0013 (6)	0.0032 (6)	−0.0016 (6)
C10	0.0167 (7)	0.0250 (9)	0.0171 (8)	−0.0035 (6)	0.0052 (6)	−0.0031 (6)
C11	0.0191 (8)	0.0336 (10)	0.0179 (8)	−0.0009 (7)	0.0037 (6)	−0.0016 (7)
C12	0.0201 (8)	0.0467 (12)	0.0243 (9)	0.0035 (8)	0.0067 (7)	−0.0028 (8)
C13	0.0228 (9)	0.0455 (12)	0.0233 (9)	−0.0048 (8)	0.0109 (7)	−0.0042 (8)
C14	0.0284 (9)	0.0344 (10)	0.0205 (9)	−0.0069 (8)	0.0083 (7)	0.0000 (8)
C15	0.0219 (8)	0.0253 (9)	0.0219 (9)	−0.0031 (7)	0.0057 (7)	−0.0009 (7)
C16	0.0222 (8)	0.0171 (8)	0.0146 (7)	0.0029 (6)	0.0052 (6)	0.0004 (6)
C17	0.0284 (9)	0.0180 (8)	0.0177 (8)	−0.0004 (7)	0.0076 (7)	−0.0005 (6)
C18	0.0355 (10)	0.0189 (8)	0.0205 (8)	0.0063 (7)	0.0076 (7)	−0.0010 (7)
C19	0.0279 (9)	0.0282 (9)	0.0209 (8)	0.0104 (8)	0.0074 (7)	0.0011 (7)
C20	0.0217 (8)	0.0292 (10)	0.0216 (9)	0.0030 (7)	0.0053 (7)	0.0008 (7)
C21	0.0241 (8)	0.0193 (8)	0.0181 (8)	0.0009 (7)	0.0061 (7)	0.0001 (6)
C22	0.0835 (18)	0.0346 (12)	0.0241 (10)	−0.0237 (12)	0.0197 (12)	−0.0027 (9)
C23	0.0472 (14)	0.093 (2)	0.0303 (12)	−0.0088 (14)	0.0127 (11)	0.0048 (13)
C24	0.222 (5)	0.0290 (13)	0.0438 (16)	−0.011 (2)	0.069 (2)	0.0036 (11)

Geometric parameters (Å, º) top

O1—C7	1.211 (2)	C9—C10	1.468 (2)
O2—C7	1.317 (2)	C10—C15	1.401 (2)
O2—H1O2	0.9032	C10—C11	1.401 (2)
O3—C11	1.364 (2)	C11—C12	1.397 (2)
O3—H1O3	0.91 (3)	C12—C13	1.382 (3)
O4—C17	1.361 (2)	C12—H12A	0.9500
O4—H1O4	1.0018	C13—C14	1.386 (3)
O5—C22	1.233 (3)	C13—H13A	0.9500
N1—C8	1.350 (2)	C14—C15	1.387 (2)
N1—N2	1.3707 (18)	C14—H14A	0.9500
N1—C4	1.427 (2)	C15—H15A	0.9500
N2—C9	1.329 (2)	C16—C21	1.393 (2)
N3—C8	1.327 (2)	C16—C17	1.401 (2)
N3—C9	1.371 (2)	C17—C18	1.394 (2)
N4—C22	1.331 (3)	C18—C19	1.382 (3)
N4—C24	1.452 (4)	C18—H18A	0.9500
N4—C23	1.454 (4)	C19—C20	1.389 (3)
C1—C6	1.387 (2)	C19—H19A	0.9500
C1—C2	1.394 (2)	C20—C21	1.389 (2)
C1—C7	1.493 (2)	C20—H20A	0.9500
C2—C3	1.390 (3)	C21—H21A	0.9500
C2—H2A	0.9500	C22—H22A	0.9500
C3—C4	1.384 (2)	C23—H23A	0.9800
C3—H3A	0.9500	C23—H23B	0.9800
C4—C5	1.389 (2)	C23—H23C	0.9800
C5—C6	1.384 (2)	C24—H24A	0.9800
C5—H5A	0.9500	C24—H24B	0.9800
C6—H6A	0.9500	C24—H24C	0.9800
C8—C16	1.477 (2)

C7—O2—H1O2	106.4	C13—C12—H12A	119.8
C11—O3—H1O3	107.8 (16)	C11—C12—H12A	119.8
C17—O4—H1O4	111.1	C12—C13—C14	120.40 (17)
C8—N1—N2	109.37 (13)	C12—C13—H13A	119.8
C8—N1—C4	129.99 (14)	C14—C13—H13A	119.8
N2—N1—C4	120.61 (13)	C13—C14—C15	119.53 (18)
C9—N2—N1	103.34 (13)	C13—C14—H14A	120.2
C8—N3—C9	103.93 (14)	C15—C14—H14A	120.2
C22—N4—C24	121.9 (2)	C14—C15—C10	121.02 (17)
C22—N4—C23	120.4 (2)	C14—C15—H15A	119.5
C24—N4—C23	117.6 (2)	C10—C15—H15A	119.5
C6—C1—C2	119.39 (16)	C21—C16—C17	120.27 (15)
C6—C1—C7	117.52 (15)	C21—C16—C8	120.88 (15)
C2—C1—C7	123.10 (16)	C17—C16—C8	118.85 (15)
C3—C2—C1	120.62 (17)	O4—C17—C18	123.84 (16)
C3—C2—H2A	119.7	O4—C17—C16	116.90 (15)
C1—C2—H2A	119.7	C18—C17—C16	119.26 (16)
C4—C3—C2	118.93 (17)	C19—C18—C17	119.96 (17)
C4—C3—H3A	120.5	C19—C18—H18A	120.0
C2—C3—H3A	120.5	C17—C18—H18A	120.0
C3—C4—C5	121.21 (16)	C18—C19—C20	121.00 (16)
C3—C4—N1	119.21 (15)	C18—C19—H19A	119.5
C5—C4—N1	119.58 (15)	C20—C19—H19A	119.5
C6—C5—C4	119.24 (16)	C19—C20—C21	119.54 (17)
C6—C5—H5A	120.4	C19—C20—H20A	120.2
C4—C5—H5A	120.4	C21—C20—H20A	120.2
C5—C6—C1	120.61 (15)	C20—C21—C16	119.95 (16)
C5—C6—H6A	119.7	C20—C21—H21A	120.0
C1—C6—H6A	119.7	C16—C21—H21A	120.0
O1—C7—O2	122.90 (17)	O5—C22—N4	124.8 (2)
O1—C7—C1	122.74 (16)	O5—C22—H22A	117.6
O2—C7—C1	114.34 (16)	N4—C22—H22A	117.6
N3—C8—N1	109.92 (14)	N4—C23—H23A	109.5
N3—C8—C16	124.90 (15)	N4—C23—H23B	109.5
N1—C8—C16	125.16 (14)	H23A—C23—H23B	109.5
N2—C9—N3	113.43 (14)	N4—C23—H23C	109.5
N2—C9—C10	122.24 (15)	H23A—C23—H23C	109.5
N3—C9—C10	124.33 (15)	H23B—C23—H23C	109.5
C15—C10—C11	118.88 (15)	N4—C24—H24A	109.5
C15—C10—C9	120.31 (15)	N4—C24—H24B	109.5
C11—C10—C9	120.80 (16)	H24A—C24—H24B	109.5
O3—C11—C12	117.17 (17)	N4—C24—H24C	109.5
O3—C11—C10	123.14 (15)	H24A—C24—H24C	109.5
C12—C11—C10	119.68 (17)	H24B—C24—H24C	109.5
C13—C12—C11	120.48 (18)

C8—N1—N2—C9	0.46 (17)	N3—C9—C10—C15	−4.8 (3)
C4—N1—N2—C9	178.81 (14)	N2—C9—C10—C11	−5.3 (3)
C6—C1—C2—C3	0.5 (3)	N3—C9—C10—C11	174.57 (16)
C7—C1—C2—C3	−179.4 (2)	C15—C10—C11—O3	178.67 (17)
C1—C2—C3—C4	0.4 (3)	C9—C10—C11—O3	−0.7 (3)
C2—C3—C4—C5	−0.6 (3)	C15—C10—C11—C12	0.0 (3)
C2—C3—C4—N1	179.67 (19)	C9—C10—C11—C12	−179.37 (17)
C8—N1—C4—C3	144.85 (19)	O3—C11—C12—C13	−179.39 (18)
N2—N1—C4—C3	−33.1 (2)	C10—C11—C12—C13	−0.6 (3)
C8—N1—C4—C5	−34.9 (3)	C11—C12—C13—C14	0.4 (3)
N2—N1—C4—C5	147.16 (16)	C12—C13—C14—C15	0.5 (3)
C3—C4—C5—C6	0.0 (3)	C13—C14—C15—C10	−1.1 (3)
N1—C4—C5—C6	179.74 (15)	C11—C10—C15—C14	0.9 (3)
C4—C5—C6—C1	0.8 (3)	C9—C10—C15—C14	−179.77 (16)
C2—C1—C6—C5	−1.1 (3)	N3—C8—C16—C21	106.5 (2)
C7—C1—C6—C5	178.80 (17)	N1—C8—C16—C21	−71.9 (2)
C6—C1—C7—O1	−6.0 (3)	N3—C8—C16—C17	−73.7 (2)
C2—C1—C7—O1	173.9 (2)	N1—C8—C16—C17	107.98 (19)
C6—C1—C7—O2	172.4 (2)	C21—C16—C17—O4	177.93 (15)
C2—C1—C7—O2	−7.7 (3)	C8—C16—C17—O4	−1.9 (2)
C9—N3—C8—N1	0.40 (18)	C21—C16—C17—C18	−1.7 (2)
C9—N3—C8—C16	−178.18 (15)	C8—C16—C17—C18	178.41 (15)
N2—N1—C8—N3	−0.56 (18)	O4—C17—C18—C19	−178.03 (17)
C4—N1—C8—N3	−178.70 (15)	C16—C17—C18—C19	1.6 (3)
N2—N1—C8—C16	178.01 (15)	C17—C18—C19—C20	−0.7 (3)
C4—N1—C8—C16	−0.1 (3)	C18—C19—C20—C21	−0.1 (3)
N1—N2—C9—N3	−0.22 (18)	C19—C20—C21—C16	0.0 (3)
N1—N2—C9—C10	179.69 (15)	C17—C16—C21—C20	0.9 (3)
C8—N3—C9—N2	−0.10 (19)	C8—C16—C21—C20	−179.18 (16)
C8—N3—C9—C10	179.99 (15)	C24—N4—C22—O5	3.3 (4)
N2—C9—C10—C15	175.33 (16)	C23—N4—C22—O5	179.7 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H1O2···O5ⁱ	0.90	1.68	2.583 (3)	173
O3—H1O3···N2	0.91 (3)	1.83 (3)	2.645 (2)	148 (2)
O4—H1O4···N3ⁱⁱ	1.00	1.79	2.7548 (19)	161
C2—H2A···O2ⁱⁱⁱ	0.95	2.51	3.340 (3)	146
C12—H12A···O1^iv	0.95	2.59	3.436 (2)	149
C15—H15A···O4^v	0.95	2.48	3.385 (2)	160
C22—H22A···O1^vi	0.95	2.42	3.085 (3)	127

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

Experimental details

Crystal data
Chemical formula	C₂₁H₁₅N₃O₄·C₃H₇NO
M_r	446.46
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	8.8172 (8), 32.669 (3), 7.6900 (7)
β (°)	94.901 (2)
V (Å³)	2207.0 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.32 × 0.25 × 0.11

Data collection
Diffractometer	Bruker APEX DUO CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2009)
T_min, T_max	0.970, 0.989
No. of measured, independent and observed [I > 2σ(I)] reflections	18347, 6379, 4384
R_int	0.038
(sin θ/λ)_max (Å⁻¹)	0.703

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.058, 0.144, 1.04
No. of reflections	6379
No. of parameters	303
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.59, −0.56

Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H1O2···O5ⁱ	0.90	1.68	2.583 (3)	173
O3—H1O3···N2	0.91 (3)	1.83 (3)	2.645 (2)	148 (2)
O4—H1O4···N3ⁱⁱ	1.00	1.79	2.7548 (19)	161
C2—H2A···O2ⁱⁱⁱ	0.95	2.51	3.340 (3)	146
C12—H12A···O1^iv	0.95	2.59	3.436 (2)	149
C15—H15A···O4^v	0.95	2.48	3.385 (2)	160
C22—H22A···O1^vi	0.95	2.42	3.085 (3)	127

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

Footnotes

‡Thomson Reuters ResearcherID: A-3561-2009.

§Thomson Reuters ResearcherID: A-5085-2009.

Acknowledgements

ASD thanks the University of Mysore for research facilities. SC thanks the Prince of Songkla University for generous support. The authors thank the Universiti Sains Malaysia for the Research University grant No. 1001/PFIZIK/811160.

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