3,6-Bis(4-chloro­phen­yl)-N1,N4-bis­(1-phenyl­eth­yl)-1,2,4,5-tetra­zine-1,4-di­carboxamide

Sun, N.-B.; Ni, J.-B.; Rao, G.-W.

doi:10.1107/S1600536812003765

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 68| Part 3| March 2012| Pages o598-o599

doi:10.1107/S1600536812003765

Open

access

3,6-Bis(4-chlorophenyl)-N¹,N⁴-bis(1-phenylethyl)-1,2,4,5-tetrazine-1,4-dicarboxamide

Na-Bo Sun,^a Jia-Bin Ni ^b and Guo-Wu Rao ^b ^*

^aCollege of Biology and Environmental Engineering, Zhejiang Shuren University, Hangzhou 310015, People's Republic of China, and ^bCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
^*Correspondence e-mail: rgw@zjut.edu.cn

(Received 20 January 2012; accepted 28 January 2012; online 4 February 2012)

In the title molecule, C₃₂H₂₈Cl₂N₆O₂, the amide-substituted N atoms of the tetrazine ring deviate from the approximate plane of the four other atoms in the ring by 0.468 (3) and 0.484 (3) Å, forming a boat conformation. The dihedral angle between the two phenyl rings is 67.0 (1)° and that between the two chloro-substituted benzene rings is 73.8 (1)°. Two intramolecular N—H⋯N hydrogen bonds are observed.

Related literature

For chemical reactions of 1,2,4,5-tetrazine derivatives, see: Domingo et al. (2009 ); Lorincz et al. (2010 ). For their biological activities, see: Devaraj et al. (2009 ); Eremeev et al. (1978 , 1980 ); Han et al. (2010 ); Neunhoeffer (1984 ); Sauer (1996 ). For anti-tumor activity of 1,2,4,5-tetrazine derivatives, see: Hu et al. (2002 , 2004 ); Rao & Hu (2005 , 2006 ). For standard bond lengths, see: Allen et al. (1987 ). For the synthesis of the title compound, see: Abdel-rahman et al. (1968 ); Hu et al. (2004); Rao & Hu (2006).

Experimental

Crystal data

C₃₂H₂₈Cl₂N₆O₂
M_r = 599.50
Orthorhombic, P 2₁ 2₁ 2₁
a = 9.715 (2) Å
b = 14.725 (3) Å
c = 21.159 (5) Å
V = 3027.0 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 298 K
0.23 × 0.19 × 0.12 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1997 ) T_min = 0.944, T_max = 0.970
19445 measured reflections
7314 independent reflections
4680 reflections with I > 2σ(I)
R_int = 0.033

Refinement

R[F² > 2σ(F²)] = 0.042
wR(F²) = 0.099
S = 1.01
7314 reflections
380 parameters
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.15 e Å⁻³
Absolute structure: Flack (1983 ), with 3185 Friedel pairs
Flack parameter: 0.03 (5)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯N2	0.86	2.21	2.613 (2)	109
N6—H6⋯N5	0.86	2.13	2.573 (2)	112

Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812003765/lh5409sup1.cif

Supporting information file. DOI: 10.1107/S1600536812003765/lh5409Isup2.cdx

Structure factors: contains datablock I. DOI: 10.1107/S1600536812003765/lh5409Isup3.hkl

Supporting information file. DOI: 10.1107/S1600536812003765/lh5409Isup4.cml

checkCIF report

Comment top

Tetrazine derivatives have high activity in chemical reactions (Domingo et al., 2009; Lorincz et al., 2010), and have been widely used in medicines and pesticides (Devaraj et al., 2009; Eremeev et al., 1978, 1980; Han et al., 2010; Neunhoeffer, 1984; Sauer, 1996). In a continuation of our studies of antitumor activities in 1,2,4,5-tetrazine derivatives (Hu et al., 2002, 2004; Rao & Hu, 2005, 2006), we have obtained a yellow crystalline compound, (I). However, IR, NMR, and MS studies failed to prove whether the substituted groups of the nitrogen are located at the 1,4 or 1,2 position. The structure was confirmed by single-crystal X-ray diffraction. The molecular structure of (I) is illustrated in Fig. 1.

The N2═C3 [1.282 (2) Å] and N5═C6 [1.285 (2) Å] bonds are typical as are the C3—N4 [1.407 (3) Å], N4—N5 [1.429 (2) Å], C6—N1 [1.396 (2) Å] and N1—N2 [1.417 (2) Å] bonds (Allen et al., 1987). The tetrazine ring is a 1,4-dihydro structure with the N-substituted groups at the 1,4-positions.

In (I), atoms N2, C3, N5 and C6 are approximately planar, with the largest deviation from this plane being 0.0236 (9) Å. Atoms N1 and N4 deviate from this plane by 0.468 (3) and 0.484 (3) Å, respectively. The dihedral angle between the N2/C3/N5/C6 plane and the N1/N2/C6 plane is 38.00 (17)°, and between the N2/C3/N5/C6 plane and the N4/N5/C3 plane is 38.81 (14)°. The tetrazine ring has a boat conformation. The dihedral angles between the N2/C3/N5/C6 plane and the two benzene rings at the 3,6-positions are 35.91 (10) and 42.87 (8)°, respectively. And the two benzene rings form a dihedral angle of 73.8 (1)°. Two intramolecular N—H···N hydrogen bonds are observed.

Related literature top

For chemical reactions of 1,2,4,5-tetrazine derivatives, see: Domingo et al. (2009); Lorincz et al. (2010). For their biological activities, see: Devaraj et al. (2009); Eremeev et al. (1978, 1980); Han et al. (2010); Neunhoeffer (1984); Sauer (1996). For anti-tumor activity of 1,2,4,5-tetrazine derivatives, see: Hu et al. (2002, 2004); Rao & Hu (2005, 2006). For standard bond lengths, see: Allen et al. (1987). For the synthesis of the title compound, see: Abdel-rahman et al. (1968); Hu et al. (2004); Rao & Hu (2006).

Experimental top

The title compound was prepared according to the procedure of Abdel-rahman et al. (1968); Hu et al. (2004); Rao & Hu, (2006). A solution of the compound in ethanol was concentrated gradually at room temperature to afford yellow blocks.

Computing details top

Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. The molecular structure of (I), shown with 30% probability displacement ellipsoids.
	Fig. 2. A portion of the crystal packing of (I). Hydrogen bonds are shown as dashed lines. H atoms not involved in hydrogen bonding were omitted for clarity.

3,6-Bis(4-chlorophenyl)-N¹,N⁴-bis(1-phenylethyl)- 1,2,4,5-tetrazine-1,4-dicarboxamide top

Crystal data top

C₃₂H₂₈Cl₂N₆O₂	F(000) = 1248
M_r = 599.50	D_x = 1.316 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 4171 reflections
a = 9.715 (2) Å	θ = 2.5–21.5°
b = 14.725 (3) Å	µ = 0.25 mm⁻¹
c = 21.159 (5) Å	T = 298 K
V = 3027.0 (12) Å³	Block, yellow
Z = 4	0.23 × 0.19 × 0.12 mm

Data collection top

Bruker SMART CCD diffractometer	7314 independent reflections
Radiation source: fine-focus sealed tube	4680 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.033
ϕ and ω scans	θ_max = 28.2°, θ_min = 1.7°
Absorption correction: multi-scan (SADABS; Bruker, 1997)	h = −12→12
T_min = 0.944, T_max = 0.970	k = −19→17
19445 measured reflections	l = −27→23

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.042	w = 1/[σ²(F_o²) + (0.0431P)²] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.099	(Δ/σ)_max < 0.001
S = 1.01	Δρ_max = 0.13 e Å⁻³
7314 reflections	Δρ_min = −0.15 e Å⁻³
380 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0032 (5)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), with 3185 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.03 (5)

Crystal data top

C₃₂H₂₈Cl₂N₆O₂	V = 3027.0 (12) Å³
M_r = 599.50	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 9.715 (2) Å	µ = 0.25 mm⁻¹
b = 14.725 (3) Å	T = 298 K
c = 21.159 (5) Å	0.23 × 0.19 × 0.12 mm

Data collection top

Bruker SMART CCD diffractometer	7314 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 1997)	4680 reflections with I > 2σ(I)
T_min = 0.944, T_max = 0.970	R_int = 0.033
19445 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.042	H-atom parameters constrained
wR(F²) = 0.099	Δρ_max = 0.13 e Å⁻³
S = 1.01	Δρ_min = −0.15 e Å⁻³
7314 reflections	Absolute structure: Flack (1983), with 3185 Friedel pairs
380 parameters	Absolute structure parameter: 0.03 (5)
0 restraints

Special details top

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.

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

	x	y	z	U_iso*/U_eq
Cl1	0.97748 (8)	0.65714 (4)	0.24050 (3)	0.0762 (2)
Cl2	1.29647 (10)	1.51972 (5)	0.14950 (5)	0.1031 (3)
O1	1.00558 (16)	0.89564 (10)	0.01136 (7)	0.0586 (4)
N2	1.06405 (18)	1.12227 (11)	0.05805 (8)	0.0481 (4)
C9	0.9347 (2)	0.92381 (13)	0.13933 (9)	0.0413 (4)
N1	0.99625 (16)	1.03724 (10)	0.05423 (7)	0.0456 (4)
C12	0.9598 (2)	0.76006 (14)	0.20118 (10)	0.0504 (5)
N4	0.85399 (17)	1.15911 (11)	0.10225 (8)	0.0458 (4)
C14	0.8196 (2)	0.87854 (15)	0.16048 (10)	0.0499 (5)
H14	0.7329	0.9036	0.1539	0.060*
N5	0.84906 (17)	1.07490 (11)	0.13578 (8)	0.0470 (4)
C6	0.92133 (19)	1.01363 (13)	0.10807 (9)	0.0422 (5)
C3	0.9867 (2)	1.18387 (13)	0.08194 (9)	0.0443 (5)
C15	1.0540 (2)	0.97121 (14)	0.01349 (9)	0.0464 (5)
C13	0.8316 (2)	0.79653 (15)	0.19127 (11)	0.0542 (6)
H13	0.7535	0.7661	0.2052	0.065*
O2	0.73843 (16)	1.29115 (10)	0.08359 (8)	0.0599 (4)
C16	0.7439 (2)	1.21948 (15)	0.11254 (10)	0.0496 (5)
C11	1.0759 (2)	0.80464 (16)	0.18125 (11)	0.0594 (6)
H11	1.1625	0.7800	0.1886	0.071*
C21	1.3807 (2)	0.92538 (15)	−0.03766 (10)	0.0486 (5)
C10	1.0625 (2)	0.88628 (15)	0.15023 (11)	0.0536 (6)
H10	1.1409	0.9166	0.1364	0.064*
C2	1.1644 (2)	1.29943 (15)	0.05976 (11)	0.0595 (6)
H2	1.1902	1.2655	0.0246	0.071*
C1	1.0499 (2)	1.27347 (13)	0.09516 (9)	0.0467 (5)
C7	1.0867 (3)	1.40218 (15)	0.16293 (11)	0.0608 (6)
H7	1.0604	1.4374	0.1973	0.073*
C22	1.4427 (3)	0.84197 (17)	−0.04630 (11)	0.0667 (7)
H22	1.3939	0.7953	−0.0657	0.080*
C27	0.5366 (2)	1.26970 (15)	0.23883 (11)	0.0546 (6)
C8	1.0115 (2)	1.32642 (13)	0.14618 (10)	0.0515 (5)
H8	0.9339	1.3108	0.1695	0.062*
N3	1.15792 (19)	1.00173 (12)	−0.02169 (9)	0.0609 (5)
H3	1.1793	1.0584	−0.0200	0.073*
C28	0.5385 (2)	1.20923 (16)	0.28849 (12)	0.0659 (7)
H28	0.5316	1.1474	0.2800	0.079*
N6	0.6510 (2)	1.18814 (14)	0.15343 (10)	0.0700 (6)
H6	0.6655	1.1360	0.1705	0.084*
C25	1.5885 (3)	0.9750 (2)	0.01361 (13)	0.0771 (8)
H25	1.6371	1.0200	0.0349	0.093*
C26	1.4546 (3)	0.99204 (16)	−0.00713 (12)	0.0654 (6)
H26	1.4150	1.0487	−0.0003	0.078*
C18	0.5259 (2)	1.23737 (17)	0.17096 (12)	0.0665 (7)
H18	0.5190	1.2910	0.1438	0.080*
C17	1.2367 (2)	0.94135 (14)	−0.06312 (10)	0.0515 (5)
H17	1.1894	0.8826	−0.0643	0.062*
C19	1.2379 (3)	0.97911 (17)	−0.12969 (12)	0.0685 (7)
H19A	1.1450	0.9886	−0.1437	0.103*
H19B	1.2829	0.9369	−0.1574	0.103*
H19C	1.2866	1.0358	−0.1302	0.103*
C5	1.2012 (3)	1.42479 (15)	0.12797 (13)	0.0647 (7)
C24	1.6486 (3)	0.8930 (2)	0.00299 (13)	0.0769 (8)
H24	1.7387	0.8823	0.0159	0.092*
C31	0.5579 (3)	1.3885 (2)	0.3163 (2)	0.0925 (10)
H31	0.5638	1.4501	0.3257	0.111*
C23	1.5758 (3)	0.8270 (2)	−0.02661 (13)	0.0766 (8)
H23	1.6164	0.7708	−0.0337	0.092*
C4	1.2394 (3)	1.37479 (17)	0.07648 (13)	0.0691 (7)
H4	1.3159	1.3917	0.0528	0.083*
C29	0.5502 (3)	1.2375 (2)	0.35034 (14)	0.0809 (8)
H29	0.5510	1.1951	0.3829	0.097*
C32	0.5464 (3)	1.36083 (17)	0.25330 (15)	0.0758 (8)
H32	0.5453	1.4039	0.2211	0.091*
C20	0.3998 (3)	1.1790 (2)	0.15957 (15)	0.0967 (10)
H20A	0.3969	1.1610	0.1160	0.145*
H20B	0.3185	1.2131	0.1696	0.145*
H20C	0.4042	1.1260	0.1859	0.145*
C30	0.5606 (3)	1.3271 (3)	0.36354 (15)	0.0865 (9)
H30	0.5695	1.3464	0.4052	0.104*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.1065 (5)	0.0540 (3)	0.0681 (4)	−0.0008 (4)	−0.0168 (4)	0.0070 (3)
Cl2	0.1104 (6)	0.0705 (5)	0.1283 (7)	−0.0315 (4)	−0.0333 (5)	−0.0013 (4)
O1	0.0634 (9)	0.0497 (8)	0.0625 (10)	−0.0088 (8)	0.0160 (8)	−0.0093 (7)
N2	0.0526 (10)	0.0440 (9)	0.0476 (10)	−0.0026 (9)	0.0097 (8)	−0.0061 (8)
C9	0.0368 (11)	0.0460 (11)	0.0410 (11)	0.0013 (9)	0.0029 (9)	−0.0042 (9)
N1	0.0480 (9)	0.0437 (9)	0.0450 (9)	−0.0011 (8)	0.0108 (8)	−0.0067 (7)
C12	0.0618 (15)	0.0495 (11)	0.0400 (12)	−0.0001 (11)	−0.0077 (11)	−0.0031 (9)
N4	0.0481 (10)	0.0448 (9)	0.0445 (10)	0.0062 (8)	0.0053 (8)	−0.0007 (8)
C14	0.0379 (11)	0.0606 (13)	0.0512 (13)	0.0000 (10)	0.0023 (10)	0.0009 (11)
N5	0.0456 (10)	0.0499 (10)	0.0454 (10)	0.0041 (8)	0.0043 (8)	−0.0036 (8)
C6	0.0336 (10)	0.0502 (12)	0.0429 (11)	0.0003 (9)	0.0001 (9)	−0.0064 (9)
C3	0.0518 (12)	0.0451 (11)	0.0360 (10)	0.0044 (10)	0.0010 (9)	−0.0016 (9)
C15	0.0469 (12)	0.0487 (12)	0.0436 (12)	0.0032 (10)	0.0036 (10)	−0.0060 (9)
C13	0.0486 (13)	0.0627 (14)	0.0512 (13)	−0.0106 (11)	0.0032 (11)	0.0041 (11)
O2	0.0657 (10)	0.0547 (9)	0.0594 (10)	0.0113 (8)	−0.0077 (8)	−0.0019 (8)
C16	0.0518 (13)	0.0567 (13)	0.0404 (12)	0.0115 (11)	−0.0057 (10)	−0.0122 (10)
C11	0.0486 (13)	0.0668 (15)	0.0627 (15)	0.0100 (12)	−0.0052 (11)	0.0035 (12)
C21	0.0541 (13)	0.0506 (13)	0.0411 (12)	−0.0066 (11)	0.0122 (10)	−0.0053 (10)
C10	0.0368 (12)	0.0618 (13)	0.0622 (15)	−0.0017 (11)	0.0019 (10)	0.0066 (11)
C2	0.0738 (16)	0.0514 (13)	0.0533 (14)	−0.0008 (12)	0.0101 (12)	0.0003 (11)
C1	0.0554 (13)	0.0428 (11)	0.0418 (11)	0.0040 (10)	−0.0035 (10)	0.0010 (9)
C7	0.0797 (18)	0.0516 (14)	0.0510 (14)	0.0029 (13)	−0.0144 (13)	−0.0077 (10)
C22	0.0734 (17)	0.0642 (15)	0.0624 (15)	0.0048 (14)	0.0004 (13)	−0.0212 (12)
C27	0.0377 (12)	0.0559 (13)	0.0701 (15)	0.0103 (10)	0.0135 (11)	0.0005 (11)
C8	0.0596 (13)	0.0488 (12)	0.0461 (12)	0.0036 (11)	−0.0039 (10)	−0.0023 (10)
N3	0.0633 (12)	0.0470 (10)	0.0723 (13)	−0.0071 (9)	0.0300 (10)	−0.0172 (9)
C28	0.0610 (16)	0.0641 (15)	0.0725 (17)	0.0094 (13)	0.0017 (13)	0.0014 (13)
N6	0.0674 (13)	0.0775 (14)	0.0650 (13)	0.0332 (11)	0.0242 (10)	0.0116 (11)
C25	0.0812 (19)	0.0749 (19)	0.0752 (19)	−0.0292 (16)	−0.0165 (15)	0.0101 (15)
C26	0.0781 (17)	0.0501 (13)	0.0680 (16)	−0.0139 (13)	−0.0007 (14)	−0.0001 (11)
C18	0.0570 (14)	0.0773 (16)	0.0650 (16)	0.0278 (13)	0.0072 (12)	0.0059 (12)
C17	0.0533 (13)	0.0464 (12)	0.0548 (14)	−0.0051 (10)	0.0149 (11)	−0.0131 (10)
C19	0.0650 (16)	0.0838 (17)	0.0566 (16)	0.0082 (14)	0.0041 (12)	−0.0089 (13)
C5	0.0740 (17)	0.0475 (13)	0.0727 (18)	−0.0043 (12)	−0.0169 (14)	0.0068 (13)
C24	0.0664 (17)	0.100 (2)	0.0646 (18)	−0.0030 (17)	−0.0029 (14)	0.0123 (16)
C31	0.0721 (19)	0.0754 (19)	0.130 (3)	0.0021 (16)	0.014 (2)	−0.036 (2)
C23	0.0709 (18)	0.0835 (19)	0.0755 (18)	0.0180 (16)	−0.0007 (14)	−0.0117 (15)
C4	0.0699 (16)	0.0597 (15)	0.0776 (19)	−0.0072 (13)	0.0082 (14)	0.0135 (13)
C29	0.0678 (17)	0.102 (2)	0.0729 (19)	0.0139 (17)	0.0053 (15)	0.0014 (17)
C32	0.0687 (17)	0.0626 (16)	0.096 (2)	0.0111 (13)	0.0218 (16)	0.0081 (15)
C20	0.0718 (18)	0.127 (3)	0.091 (2)	0.0209 (19)	−0.0122 (16)	−0.032 (2)
C30	0.0590 (16)	0.119 (3)	0.082 (2)	0.0147 (19)	0.0102 (15)	−0.026 (2)

Geometric parameters (Å, º) top

Cl1—C12	1.737 (2)	C22—H22	0.9300
Cl2—C5	1.737 (3)	C27—C28	1.378 (3)
O1—C15	1.209 (2)	C27—C32	1.380 (3)
N2—C3	1.282 (2)	C27—C18	1.516 (3)
N2—N1	1.417 (2)	C8—H8	0.9300
C9—C14	1.376 (3)	N3—C17	1.465 (3)
C9—C10	1.379 (3)	N3—H3	0.8600
C9—C6	1.485 (3)	C28—C29	1.378 (4)
N1—C6	1.396 (2)	C28—H28	0.9300
N1—C15	1.415 (2)	N6—C18	1.463 (3)
C12—C11	1.371 (3)	N6—H6	0.8600
C12—C13	1.373 (3)	C25—C24	1.359 (4)
N4—C3	1.407 (3)	C25—C26	1.396 (4)
N4—C16	1.408 (3)	C25—H25	0.9300
N4—N5	1.429 (2)	C26—H26	0.9300
C14—C13	1.377 (3)	C18—C20	1.516 (4)
C14—H14	0.9300	C18—H18	0.9800
N5—C6	1.285 (2)	C17—C19	1.514 (3)
C3—C1	1.482 (3)	C17—H17	0.9800
C15—N3	1.332 (3)	C19—H19A	0.9600
C13—H13	0.9300	C19—H19B	0.9600
O2—C16	1.221 (2)	C19—H19C	0.9600
C16—N6	1.332 (3)	C5—C4	1.366 (4)
C11—C10	1.376 (3)	C24—C23	1.355 (4)
C11—H11	0.9300	C24—H24	0.9300
C21—C26	1.377 (3)	C31—C30	1.348 (4)
C21—C22	1.380 (3)	C31—C32	1.399 (4)
C21—C17	1.517 (3)	C31—H31	0.9300
C10—H10	0.9300	C23—H23	0.9300
C2—C4	1.374 (3)	C4—H4	0.9300
C2—C1	1.395 (3)	C29—C30	1.352 (4)
C2—H2	0.9300	C29—H29	0.9300
C1—C8	1.383 (3)	C32—H32	0.9300
C7—C5	1.377 (4)	C20—H20A	0.9600
C7—C8	1.380 (3)	C20—H20B	0.9600
C7—H7	0.9300	C20—H20C	0.9600
C22—C23	1.376 (4)	C30—H30	0.9300

C3—N2—N1	112.04 (16)	C17—N3—H3	119.1
C14—C9—C10	118.89 (18)	C27—C28—C29	122.0 (2)
C14—C9—C6	120.35 (18)	C27—C28—H28	119.0
C10—C9—C6	120.69 (18)	C29—C28—H28	119.0
C6—N1—C15	122.19 (16)	C16—N6—C18	123.7 (2)
C6—N1—N2	114.56 (15)	C16—N6—H6	118.1
C15—N1—N2	117.23 (15)	C18—N6—H6	118.1
C11—C12—C13	120.78 (19)	C24—C25—C26	120.5 (3)
C11—C12—Cl1	118.95 (17)	C24—C25—H25	119.7
C13—C12—Cl1	120.26 (18)	C26—C25—H25	119.7
C3—N4—C16	125.43 (17)	C21—C26—C25	120.3 (2)
C3—N4—N5	114.03 (15)	C21—C26—H26	119.8
C16—N4—N5	116.47 (16)	C25—C26—H26	119.8
C9—C14—C13	120.7 (2)	N6—C18—C20	110.5 (2)
C9—C14—H14	119.7	N6—C18—C27	109.80 (19)
C13—C14—H14	119.7	C20—C18—C27	112.6 (2)
C6—N5—N4	111.37 (16)	N6—C18—H18	107.9
N5—C6—N1	118.85 (17)	C20—C18—H18	107.9
N5—C6—C9	118.05 (18)	C27—C18—H18	107.9
N1—C6—C9	122.67 (16)	N3—C17—C19	109.74 (19)
N2—C3—N4	118.31 (17)	N3—C17—C21	111.32 (18)
N2—C3—C1	117.47 (18)	C19—C17—C21	112.34 (18)
N4—C3—C1	123.57 (18)	N3—C17—H17	107.7
O1—C15—N3	125.77 (19)	C19—C17—H17	107.7
O1—C15—N1	120.04 (18)	C21—C17—H17	107.7
N3—C15—N1	114.14 (18)	C17—C19—H19A	109.5
C12—C13—C14	119.5 (2)	C17—C19—H19B	109.5
C12—C13—H13	120.3	H19A—C19—H19B	109.5
C14—C13—H13	120.3	C17—C19—H19C	109.5
O2—C16—N6	126.6 (2)	H19A—C19—H19C	109.5
O2—C16—N4	120.1 (2)	H19B—C19—H19C	109.5
N6—C16—N4	113.33 (19)	C4—C5—C7	121.2 (2)
C12—C11—C10	119.2 (2)	C4—C5—Cl2	119.9 (2)
C12—C11—H11	120.4	C7—C5—Cl2	119.0 (2)
C10—C11—H11	120.4	C23—C24—C25	119.3 (3)
C26—C21—C22	118.0 (2)	C23—C24—H24	120.4
C26—C21—C17	122.4 (2)	C25—C24—H24	120.4
C22—C21—C17	119.5 (2)	C30—C31—C32	120.8 (3)
C11—C10—C9	121.0 (2)	C30—C31—H31	119.6
C11—C10—H10	119.5	C32—C31—H31	119.6
C9—C10—H10	119.5	C24—C23—C22	121.0 (3)
C4—C2—C1	120.4 (2)	C24—C23—H23	119.5
C4—C2—H2	119.8	C22—C23—H23	119.5
C1—C2—H2	119.8	C5—C4—C2	119.8 (2)
C8—C1—C2	118.7 (2)	C5—C4—H4	120.1
C8—C1—C3	122.51 (19)	C2—C4—H4	120.1
C2—C1—C3	118.25 (19)	C30—C29—C28	119.8 (3)
C5—C7—C8	119.0 (2)	C30—C29—H29	120.1
C5—C7—H7	120.5	C28—C29—H29	120.1
C8—C7—H7	120.5	C27—C32—C31	120.0 (3)
C23—C22—C21	120.8 (2)	C27—C32—H32	120.0
C23—C22—H22	119.6	C31—C32—H32	120.0
C21—C22—H22	119.6	C18—C20—H20A	109.5
C28—C27—C32	117.3 (2)	C18—C20—H20B	109.5
C28—C27—C18	121.4 (2)	H20A—C20—H20B	109.5
C32—C27—C18	121.3 (2)	C18—C20—H20C	109.5
C7—C8—C1	120.9 (2)	H20A—C20—H20C	109.5
C7—C8—H8	119.6	H20B—C20—H20C	109.5
C1—C8—H8	119.6	C31—C30—C29	120.0 (3)
C15—N3—C17	121.72 (18)	C31—C30—H30	120.0
C15—N3—H3	119.1	C29—C30—H30	120.0

C3—N2—N1—C6	−43.9 (2)	N2—C3—C1—C2	25.8 (3)
C3—N2—N1—C15	162.73 (18)	N4—C3—C1—C2	−163.65 (19)
C10—C9—C14—C13	−0.9 (3)	C26—C21—C22—C23	−1.9 (3)
C6—C9—C14—C13	−177.96 (19)	C17—C21—C22—C23	176.6 (2)
C3—N4—N5—C6	−44.5 (2)	C5—C7—C8—C1	0.1 (3)
C16—N4—N5—C6	156.90 (17)	C2—C1—C8—C7	−1.7 (3)
N4—N5—C6—N1	3.2 (2)	C3—C1—C8—C7	169.61 (19)
N4—N5—C6—C9	175.90 (16)	O1—C15—N3—C17	−7.2 (4)
C15—N1—C6—N5	−166.24 (18)	N1—C15—N3—C17	175.42 (19)
N2—N1—C6—N5	41.9 (2)	C32—C27—C28—C29	−0.3 (4)
C15—N1—C6—C9	21.4 (3)	C18—C27—C28—C29	179.0 (2)
N2—N1—C6—C9	−130.45 (18)	O2—C16—N6—C18	−1.1 (4)
C14—C9—C6—N5	50.0 (3)	N4—C16—N6—C18	−178.7 (2)
C10—C9—C6—N5	−127.1 (2)	C22—C21—C26—C25	0.7 (3)
C14—C9—C6—N1	−137.6 (2)	C17—C21—C26—C25	−177.9 (2)
C10—C9—C6—N1	45.3 (3)	C24—C25—C26—C21	1.1 (4)
N1—N2—C3—N4	2.3 (2)	C16—N6—C18—C20	124.9 (3)
N1—N2—C3—C1	173.40 (16)	C16—N6—C18—C27	−110.3 (3)
C16—N4—C3—N2	−161.03 (18)	C28—C27—C18—N6	−67.0 (3)
N5—N4—C3—N2	42.6 (2)	C32—C27—C18—N6	112.3 (3)
C16—N4—C3—C1	28.5 (3)	C28—C27—C18—C20	56.6 (3)
N5—N4—C3—C1	−127.88 (18)	C32—C27—C18—C20	−124.1 (3)
C6—N1—C15—O1	24.2 (3)	C15—N3—C17—C19	126.1 (2)
N2—N1—C15—O1	175.37 (18)	C15—N3—C17—C21	−108.9 (2)
C6—N1—C15—N3	−158.24 (18)	C26—C21—C17—N3	−36.0 (3)
N2—N1—C15—N3	−7.0 (3)	C22—C21—C17—N3	145.54 (19)
C11—C12—C13—C14	0.5 (3)	C26—C21—C17—C19	87.6 (2)
Cl1—C12—C13—C14	179.46 (16)	C22—C21—C17—C19	−90.9 (2)
C9—C14—C13—C12	0.4 (3)	C8—C7—C5—C4	1.4 (4)
C3—N4—C16—O2	27.1 (3)	C8—C7—C5—Cl2	−179.52 (17)
N5—N4—C16—O2	−177.10 (18)	C26—C25—C24—C23	−1.7 (4)
C3—N4—C16—N6	−155.15 (19)	C25—C24—C23—C22	0.4 (4)
N5—N4—C16—N6	0.7 (2)	C21—C22—C23—C24	1.5 (4)
C13—C12—C11—C10	−0.9 (3)	C7—C5—C4—C2	−1.4 (4)
Cl1—C12—C11—C10	−179.83 (17)	Cl2—C5—C4—C2	179.60 (18)
C12—C11—C10—C9	0.4 (3)	C1—C2—C4—C5	−0.3 (4)
C14—C9—C10—C11	0.5 (3)	C27—C28—C29—C30	−0.1 (4)
C6—C9—C10—C11	177.59 (19)	C28—C27—C32—C31	0.1 (4)
C4—C2—C1—C8	1.7 (3)	C18—C27—C32—C31	−179.2 (2)
C4—C2—C1—C3	−169.9 (2)	C30—C31—C32—C27	0.4 (4)
N2—C3—C1—C8	−145.6 (2)	C32—C31—C30—C29	−0.9 (5)
N4—C3—C1—C8	25.0 (3)	C28—C29—C30—C31	0.7 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···N2	0.86	2.21	2.613 (2)	109
N6—H6···N5	0.86	2.13	2.573 (2)	112

Experimental details

Crystal data
Chemical formula	C₃₂H₂₈Cl₂N₆O₂
M_r	599.50
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	298
a, b, c (Å)	9.715 (2), 14.725 (3), 21.159 (5)
V (Å³)	3027.0 (12)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.25
Crystal size (mm)	0.23 × 0.19 × 0.12

Data collection
Diffractometer	Bruker SMART CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 1997)
T_min, T_max	0.944, 0.970
No. of measured, independent and observed [I > 2σ(I)] reflections	19445, 7314, 4680
R_int	0.033
(sin θ/λ)_max (Å⁻¹)	0.666

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.099, 1.01
No. of reflections	7314
No. of parameters	380
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.13, −0.15
Absolute structure	Flack (1983), with 3185 Friedel pairs
Absolute structure parameter	0.03 (5)

Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···N2	0.86	2.21	2.613 (2)	108.8
N6—H6···N5	0.86	2.13	2.573 (2)	111.7

Acknowledgements

The authors are very grateful to the Natural Science Foundation of Zhejiang Province (grant No. Y2090985) and the National Natural Science Foundation of China (grant No. 20802069) for financial support.

References

Abdel, N. O., Kira, M. A. & Tolba, M. N. (1968). Tetrahedron Lett. 9, 3871–3872. CrossRef Google Scholar
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L. & Orpen, A. G. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19. CrossRef Google Scholar
Bruker (1997). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Devaraj, N. K., Upadhyay, R., Haun, J. B., Hilderbrand, S. A. & Weissleder, R. (2009). Angew. Chem. Int. Ed. 48, 7013–7016. Web of Science CrossRef CAS Google Scholar
Domingo, L. R., Picher, M. T. & Saez, J. A. (2009). J. Org. Chem. 74, 2726–2735. Web of Science CrossRef PubMed CAS Google Scholar
Eremeev, A. V., Tikhomirova, D. A. & Zidermane, A. (1980). USSR Patent No. 686336. Google Scholar
Eremeev, A. V., Tikhomirv, D. A., Tyusheva, V. A. & Liepins, F. (1978). Khim. Geterotsikl. Soedin. 6, 753–757. Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Han, H. S., Devaraj, N. K., Lee, J., Hilderbrand, S. A., Weissleder, R. & Bawendi, M. G. (2010). J. Am. Chem. Soc. 132, 7838–7839. Web of Science CrossRef CAS PubMed Google Scholar
Hu, W. X., Rao, G. W. & Sun, Y. Q. (2004). Bioorg. Med. Chem. Lett. 14, 1177–1181. Web of Science CSD CrossRef PubMed CAS Google Scholar
Hu, W. X., Sun, Y. Q., Yuan, Q. & Yang, Z. Y. (2002). Chem. J. Chin. Univ. 23, 1877–1881. CAS Google Scholar
Lorincz, K., Kotschy, A., Tammiku-Taul, J., Sikk, L. & Burk, P. (2010). J. Org. Chem. 75, 6196–6200. Web of Science CAS PubMed Google Scholar
Neunhoeffer, H. (1984). Comprehensive Heterocyclic Chemistry, 1st ed., edited by A. R. Katritzky, Vol. 3, pp. 531–572. Frankfurt: Pergamon. Google Scholar
Rao, G. W. & Hu, W. X. (2005). Bioorg. Med. Chem. Lett. 15, 3174–3176. Web of Science CSD CrossRef PubMed CAS Google Scholar
Rao, G. W. & Hu, W. X. (2006). Bioorg. Med. Chem. Lett. 16, 3702–3705. Web of Science CSD CrossRef PubMed CAS Google Scholar
Sauer, J. (1996). Comprehensive Heterocyclic Chemistry, 2nd ed., edited by A. J. Boulton, Vol. 6, pp. 901–955. Oxford: Elsevier. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.