10,10′-Methyl­enebis[2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)-dione] dihydrate

Benzeid, H.; Saffon, N.; Garrigues, B.; Essassi, E.M.; Ng, S.W.

doi:10.1107/S1600536809040501

organic compounds

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Volume 65| Part 11| November 2009| Page o2684

https://doi.org/10.1107/S1600536809040501

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10,10′-Methylenebis[2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)-dione] dihydrate

Hanane Benzeid,^a Nathalie Saffon,^b Bernard Garrigues,^c El Mokhtar Essassi ^a and Seik Weng Ng ^d ^*

^aLaboratoire de Chimie Organique Hétérocyclique, Pôle de Compétences Pharmacochimie, Université Mohammed V-Agdal, BP 1014 Avenue Ibn Batout, Rabat, Morocco, ^bService Commun Rayons X, Université Paul Sabatier, Bâtiment 2R1, 118 route de Narbonne, 31062 Toulouse, France, ^cHétérochimie Fondamentale et Appliquée, Université Paul Sabatier, UMR 5069, 118 Route de Narbonne, 31062 Toulouse, France, and ^dDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
^*Correspondence e-mail: seikweng@um.edu.my

(Received 29 September 2009; accepted 5 October 2009; online 10 October 2009)

The organic molecule and uncoordinated water molecule in the crystal of the title compound, C₂₅H₂₄N₄O₄·2H₂O, both lie on special positions of twofold symmetry. A twofold rotation axis passes through the methylene C atom connecting the two dihydrobenzopyrrolodiazepindionyl parts. The seven-membered C₅N₂ ring adopts a boat conformation.

Related literature

Pyrrolo[2,1-c][1,4]benzodiazepines are a group of potent chemicals produced by Streptomyces species. For their anti-cancer activity, see: Bose et al. (1992 ); Cargill et al. (1974 ); Gregson et al. (2004 ).

Experimental

Crystal data

C₂₅H₂₄N₄O₄·2H₂O
M_r = 480.51
Trigonal, P 3₁ 21
a = 11.9901 (2) Å
c = 13.6054 (2) Å
V = 1693.90 (4) Å³
Z = 3
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 193 K
0.20 × 0.20 × 0.10 mm

Data collection

Bruker APEXII diffractometer
Absorption correction: none
23041 measured reflections
1572 independent reflections
1472 reflections with I > 2σ(I)
R_int = 0.043

Refinement

R[F² > 2σ(F²)] = 0.043
wR(F²) = 0.126
S = 1.18
1572 reflections
159 parameters
H-atom parameters constrained
Δρ_max = 0.46 e Å⁻³
Δρ_min = −0.48 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT; 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: publCIF (Westrip, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536809040501/tk2545sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536809040501/tk2545Isup2.hkl

checkCIF report

Related literature top

Pyrrolo[2,1-c][1,4]benzodiazepines are a group of potent chemicals produced by Streptomyces species. For their anti-cancer activity, see: Bose et al. (1992); Cargill et al. (1974); Gregson et al. (2004).

Experimental top

2,3-Dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)-dione (1.1 g, 6 mmol), dibromomethane (1.8 ml, 2.54 mmol), potassium carbonate (0.71 g, 6 mmol) and a catalytic quantity of tetra-n-butylammonium bromide were stirred in N,N-dimethylformamide (20 ml) for 24 h. The insoluble salts were filtered off and the solvent was removed under vacuum. The residue was separated by chromatography on silica gel with an n-hexane:ethyl acetate (8:2) solvent system. The compound was obtained as colorless crystals in 70% yield upon evaporation of the solvent.

Structure description top

Pyrrolo[2,1-c][1,4]benzodiazepines are a group of potent chemicals produced by Streptomyces species. For their anti-cancer activity, see: Bose et al. (1992); Cargill et al. (1974); Gregson et al. (2004).

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); 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: publCIF (Westrip, 2009).

Figures top

Fig. 1. Thermal ellipsoid plot (Barbour, 2001) of C₂₅H₂₄N₄O₄^.H₂O at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius. Unlabelled atoms are related by a twofold axis.

10,10'-Methylenebis[2,3-dihydro-1H- benzo[e]pyrrolo[1,2-a][1,4]diazepine- 5,11(10H,11aH)-dione] dihydrate top

Crystal data top

C₂₅H₂₄N₄O₄·2H₂O	D_x = 1.413 Mg m⁻³
M_r = 480.51	Mo Kα radiation, λ = 0.71073 Å
Trigonal, P3₁21	Cell parameters from 9284 reflections
Hall symbol: P 31 2"	θ = 5.0–28.3°
a = 11.9901 (2) Å	µ = 0.10 mm⁻¹
c = 13.6054 (2) Å	T = 193 K
V = 1693.90 (4) Å³	Block, colorless
Z = 3	0.20 × 0.20 × 0.10 mm
F(000) = 762

Data collection top

Bruker APEXII diffractometer	1472 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.043
Graphite monochromator	θ_max = 28.3°, θ_min = 5.2°
φ and ω scans	h = −13→0
23041 measured reflections	k = 0→15
1572 independent reflections	l = 0→18

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.043	H-atom parameters constrained
wR(F²) = 0.126	w = 1/[σ²(F_o²) + (0.0716P)² + 0.3837P] where P = (F_o² + 2F_c²)/3
S = 1.18	(Δ/σ)_max = 0.001
1572 reflections	Δρ_max = 0.46 e Å⁻³
159 parameters	Δρ_min = −0.48 e Å⁻³
0 restraints	Absolute structure: nd
Primary atom site location: structure-invariant direct methods

Crystal data top

C₂₅H₂₄N₄O₄·2H₂O	Z = 3
M_r = 480.51	Mo Kα radiation
Trigonal, P3₁21	µ = 0.10 mm⁻¹
a = 11.9901 (2) Å	T = 193 K
c = 13.6054 (2) Å	0.20 × 0.20 × 0.10 mm
V = 1693.90 (4) Å³

Data collection top

Bruker APEXII diffractometer	1472 reflections with I > 2σ(I)
23041 measured reflections	R_int = 0.043
1572 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	0 restraints
wR(F²) = 0.126	H-atom parameters constrained
S = 1.18	Δρ_max = 0.46 e Å⁻³
1572 reflections	Δρ_min = −0.48 e Å⁻³
159 parameters	Absolute structure: nd

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	0.57170 (18)	0.14709 (17)	0.22350 (11)	0.0274 (4)
O2	0.7198 (2)	0.0623 (2)	0.57106 (13)	0.0362 (5)
O1W	0.9339 (4)	0.0162 (4)	0.5795 (2)	0.0819 (10)
H1W1	0.8758	0.0349	0.5692	0.123*
H1W2	1.0069	0.0798	0.5645	0.123*
N1	0.47771 (19)	0.1028 (2)	0.37359 (13)	0.0219 (4)
N2	0.7341 (2)	0.16144 (19)	0.42630 (14)	0.0235 (4)
C1	0.4814 (2)	0.1364 (2)	0.47532 (15)	0.0233 (5)
C2	0.3891 (3)	0.1666 (3)	0.50682 (18)	0.0303 (5)
H2	0.3310	0.1689	0.4606	0.036*
C3	0.3812 (3)	0.1934 (3)	0.60537 (19)	0.0361 (6)
H3	0.3195	0.2160	0.6261	0.043*
C4	0.4645 (3)	0.1867 (3)	0.67300 (18)	0.0382 (7)
H4	0.4581	0.2019	0.7407	0.046*
C5	0.5571 (3)	0.1577 (2)	0.64133 (16)	0.0303 (6)
H5	0.6133	0.1529	0.6882	0.036*
C6	0.5699 (2)	0.1355 (2)	0.54191 (16)	0.0243 (5)
C7	0.3561 (3)	0.0000	0.3333	0.0239 (6)
H7A	0.2900	−0.0353	0.3858	0.029*	0.50
H7B	0.3253	0.0353	0.2809	0.029*	0.50
C8	0.5813 (2)	0.1646 (2)	0.31219 (16)	0.0224 (5)
C9	0.7077 (2)	0.2487 (2)	0.36580 (15)	0.0225 (5)
H9	0.7020	0.3141	0.4078	0.027*
C10	0.8238 (2)	0.3128 (3)	0.29721 (17)	0.0296 (5)
H10A	0.8938	0.3930	0.3265	0.036*
H10B	0.7997	0.3332	0.2329	0.036*
C11	0.8645 (3)	0.2109 (3)	0.28641 (18)	0.0320 (6)
H11A	0.9549	0.2499	0.2641	0.038*
H11B	0.8080	0.1425	0.2397	0.038*
C12	0.8482 (3)	0.1579 (3)	0.39173 (18)	0.0317 (6)
H12A	0.8334	0.0690	0.3918	0.038*
H12B	0.9245	0.2133	0.4327	0.038*
C13	0.6801 (2)	0.1157 (2)	0.51428 (16)	0.0251 (5)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0330 (9)	0.0290 (9)	0.0170 (7)	0.0132 (8)	−0.0008 (6)	0.0000 (6)
O2	0.0427 (11)	0.0404 (11)	0.0284 (9)	0.0229 (9)	−0.0039 (8)	0.0068 (8)
O1W	0.082 (2)	0.126 (3)	0.0681 (18)	0.075 (2)	−0.0051 (16)	0.0110 (19)
N1	0.0235 (9)	0.0246 (9)	0.0173 (8)	0.0117 (8)	−0.0014 (7)	−0.0033 (7)
N2	0.0260 (10)	0.0253 (10)	0.0196 (8)	0.0131 (8)	−0.0018 (7)	0.0005 (7)
C1	0.0273 (11)	0.0201 (10)	0.0184 (9)	0.0088 (9)	0.0018 (9)	−0.0020 (8)
C2	0.0304 (13)	0.0304 (12)	0.0296 (12)	0.0148 (11)	0.0025 (9)	−0.0054 (10)
C3	0.0323 (13)	0.0361 (14)	0.0334 (13)	0.0122 (12)	0.0061 (11)	−0.0124 (11)
C4	0.0365 (15)	0.0363 (14)	0.0242 (11)	0.0050 (12)	0.0091 (11)	−0.0074 (10)
C5	0.0330 (13)	0.0259 (12)	0.0178 (10)	0.0042 (10)	0.0009 (9)	0.0005 (9)
C6	0.0267 (11)	0.0209 (10)	0.0181 (10)	0.0064 (9)	0.0014 (8)	−0.0009 (8)
C7	0.0248 (11)	0.0276 (16)	0.0203 (13)	0.0138 (8)	−0.0021 (6)	−0.0041 (12)
C8	0.0271 (11)	0.0212 (10)	0.0206 (10)	0.0134 (9)	−0.0005 (8)	0.0010 (8)
C9	0.0271 (11)	0.0212 (10)	0.0173 (9)	0.0106 (9)	−0.0013 (8)	0.0014 (8)
C10	0.0287 (12)	0.0278 (12)	0.0247 (10)	0.0084 (10)	0.0034 (9)	0.0017 (9)
C11	0.0294 (12)	0.0387 (14)	0.0277 (12)	0.0168 (11)	0.0022 (10)	−0.0014 (11)
C12	0.0299 (13)	0.0382 (14)	0.0287 (12)	0.0183 (11)	−0.0029 (10)	−0.0031 (10)
C13	0.0293 (12)	0.0227 (11)	0.0193 (9)	0.0099 (9)	−0.0037 (9)	0.0002 (8)

Geometric parameters (Å, º) top

O1—C8	1.220 (3)	C5—C6	1.402 (3)
O2—C13	1.240 (3)	C5—H5	0.9500
O1W—H1W1	0.8429	C6—C13	1.502 (4)
O1W—H1W2	0.8500	C7—N1ⁱ	1.466 (3)
N1—C8	1.367 (3)	C7—H7A	0.9900
N1—C1	1.436 (3)	C7—H7B	0.9900
N1—C7	1.466 (3)	C8—C9	1.522 (3)
N2—C13	1.341 (3)	C9—C10	1.526 (3)
N2—C12	1.466 (3)	C9—H9	1.0000
N2—C9	1.485 (3)	C10—C11	1.533 (4)
C1—C2	1.393 (3)	C10—H10A	0.9900
C1—C6	1.399 (3)	C10—H10B	0.9900
C2—C3	1.393 (3)	C11—C12	1.540 (3)
C2—H2	0.9500	C11—H11A	0.9900
C3—C4	1.389 (4)	C11—H11B	0.9900
C3—H3	0.9500	C12—H12A	0.9900
C4—C5	1.387 (4)	C12—H12B	0.9900
C4—H4	0.9500

H1W1—O1W—H1W2	109.8	O1—C8—N1	121.9 (2)
C8—N1—C1	122.97 (19)	O1—C8—C9	124.4 (2)
C8—N1—C7	118.68 (17)	N1—C8—C9	113.59 (18)
C1—N1—C7	118.32 (17)	N2—C9—C8	106.93 (18)
C13—N2—C12	122.8 (2)	N2—C9—C10	103.41 (19)
C13—N2—C9	123.6 (2)	C8—C9—C10	113.32 (18)
C12—N2—C9	111.90 (18)	N2—C9—H9	111.0
C2—C1—C6	120.4 (2)	C8—C9—H9	111.0
C2—C1—N1	116.9 (2)	C10—C9—H9	111.0
C6—C1—N1	122.6 (2)	C9—C10—C11	103.3 (2)
C1—C2—C3	120.7 (2)	C9—C10—H10A	111.1
C1—C2—H2	119.6	C11—C10—H10A	111.1
C3—C2—H2	119.6	C9—C10—H10B	111.1
C4—C3—C2	119.4 (3)	C11—C10—H10B	111.1
C4—C3—H3	120.3	H10A—C10—H10B	109.1
C2—C3—H3	120.3	C10—C11—C12	102.4 (2)
C5—C4—C3	119.8 (2)	C10—C11—H11A	111.3
C5—C4—H4	120.1	C12—C11—H11A	111.3
C3—C4—H4	120.1	C10—C11—H11B	111.3
C4—C5—C6	121.6 (2)	C12—C11—H11B	111.3
C4—C5—H5	119.2	H11A—C11—H11B	109.2
C6—C5—H5	119.2	N2—C12—C11	102.4 (2)
C1—C6—C5	117.9 (2)	N2—C12—H12A	111.3
C1—C6—C13	124.7 (2)	C11—C12—H12A	111.3
C5—C6—C13	117.4 (2)	N2—C12—H12B	111.3
N1ⁱ—C7—N1	109.8 (3)	C11—C12—H12B	111.3
N1ⁱ—C7—H7A	109.7	H12A—C12—H12B	109.2
N1—C7—H7A	109.7	O2—C13—N2	122.4 (2)
N1ⁱ—C7—H7B	109.7	O2—C13—C6	121.4 (2)
N1—C7—H7B	109.7	N2—C13—C6	116.2 (2)
H7A—C7—H7B	108.2

C8—N1—C1—C2	124.6 (2)	C12—N2—C9—C8	113.4 (2)
C7—N1—C1—C2	−53.5 (3)	C13—N2—C9—C10	158.9 (2)
C8—N1—C1—C6	−57.4 (3)	C12—N2—C9—C10	−6.5 (2)
C7—N1—C1—C6	124.5 (2)	O1—C8—C9—N2	−112.1 (2)
C6—C1—C2—C3	−1.6 (4)	N1—C8—C9—N2	64.2 (2)
N1—C1—C2—C3	176.4 (2)	O1—C8—C9—C10	1.1 (3)
C1—C2—C3—C4	−1.6 (4)	N1—C8—C9—C10	177.5 (2)
C2—C3—C4—C5	2.1 (4)	N2—C9—C10—C11	29.1 (2)
C3—C4—C5—C6	0.4 (4)	C8—C9—C10—C11	−86.3 (2)
C2—C1—C6—C5	4.0 (3)	C9—C10—C11—C12	−40.6 (2)
N1—C1—C6—C5	−173.9 (2)	C13—N2—C12—C11	175.9 (2)
C2—C1—C6—C13	−174.4 (2)	C9—N2—C12—C11	−18.6 (3)
N1—C1—C6—C13	7.7 (4)	C10—C11—C12—N2	35.9 (2)
C4—C5—C6—C1	−3.4 (4)	C12—N2—C13—O2	−3.0 (4)
C4—C5—C6—C13	175.1 (2)	C9—N2—C13—O2	−166.9 (2)
C8—N1—C7—N1ⁱ	59.77 (17)	C12—N2—C13—C6	175.5 (2)
C1—N1—C7—N1ⁱ	−122.0 (2)	C9—N2—C13—C6	11.7 (3)
C1—N1—C8—O1	−169.7 (2)	C1—C6—C13—O2	−148.6 (2)
C7—N1—C8—O1	8.4 (3)	C5—C6—C13—O2	33.0 (3)
C1—N1—C8—C9	13.9 (3)	C1—C6—C13—N2	32.9 (3)
C7—N1—C8—C9	−168.02 (19)	C5—C6—C13—N2	−145.5 (2)
C13—N2—C9—C8	−81.2 (3)

Symmetry code: (i) x−y, −y, −z+2/3.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1w—H1w1···O2	0.84	2.06	2.886 (4)	168

Experimental details

Crystal data
Chemical formula	C₂₅H₂₄N₄O₄·2H₂O
M_r	480.51
Crystal system, space group	Trigonal, P3₁21
Temperature (K)	193
a, c (Å)	11.9901 (2), 13.6054 (2)
V (Å³)	1693.90 (4)
Z	3
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.20 × 0.20 × 0.10

Data collection
Diffractometer	Bruker APEXII
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	23041, 1572, 1472
R_int	0.043
(sin θ/λ)_max (Å⁻¹)	0.667

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.126, 1.18
No. of reflections	1572
No. of parameters	159
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.46, −0.48
Absolute structure	Nd

Computer programs: APEX2 (Bruker, 2005), SAINT (Bruker, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), X-SEED (Barbour, 2001), publCIF (Westrip, 2009).

Acknowledgements

We thank Université Mohammed V-Agdal and the University of Malaya for supporting this study.

References

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