Diéthyl 10-chloro-7-méthyl-6-oxo-11b-phényl-2,3,5,6,7,11b-héxa­hydro­oxazolino[3,2-d][1,4]benzodiazépine-2,3-carboxylate

The structure of the title compound, C₂₄H₂₅ClN₂O₆, has been established and the central seven-membered ring is fused to chlorobenzo and oxazolino rings to form the core of the molecule.

S1. Comment

Dans le cadre de la synthèse de nouvelles 1,4-benzodiazépines possédant un cycle supplémentaire (Benelbaghdadi et al., 1997, 1998) et pouvant présenter une activité biologique (De Sarro & Chimirri, 1996), nous avons étudié la réaction de la condensation de la 7-chloro-1-méthyl-5-phényl-1,4-benzodiazépin-2-one, (I), avec le diazoacétate d'éthyle (DAE) (Zhu & Espenson, 1995) en présence d'acétylacétonate de cuivre [Cu(acac)₂] comme catalyseur (Fraille et al., 1996). Ainsi une addition lente du DAE catalysée sur la benzodiazépine (I) en solution dans le dichloroéthane, à une température de 308 K conduit à un seul produit (II) avec un rendement de 33%.

Les analyses spectroscopiques (RMN à haute résolution mono et bidimensionnelle) n'ayant pas permis d'attribuer à ce composé de condensation sa structure exacte, l'analyse de la structure cristalline par rayons-X a été entreprize. Cette étude a finalement conclu en faveur de la structure (II) et précize la stéréochimie de la molécule. On en déduit que le produit (II) provient d'une condensation entre la benzodiazépine (I) et le 2,3-époxybutan-1,4-dioate d'éthyle (l'époxyde du fumarate d'éthyle). Ce dernier peut être formé à partir du fumarate d'éthyle (dimère du DAE) par action de l'oxygène de l'air en présence d'un catalyseur (Budnik & Kochi, 1976; Heumann et al., 1982). Il est à signaler que la dimérization du DAE a été notée dans plusieurs travaux (Krieger & Landgrebe, 1978; Shapiro et al., 1994). Dans cette structure, la chlorobenzodiazépine-one comporte un cycle oxazoline fusionné sur le cycle à (7) chaînons. La partie benzodiazépine comporte un fragment quasi-plan: le cycle chlorophényl Cl1/C8/C9/C10/C11/C12/C13 [r.m.s. d/'eviation: 0.003 (2) Å] et le plan formé par les quatre atomes N7/C8/C13/C14 [r.m.s. déviation 0.001 (2) Å], l'angle entre ces deux plans est: 0.69 (3)°. La déformation du cycle diazépine est donnée par les angles de torsion C14/N4/C5/C6 [−55.5 (3)°] et N4/C5/C6/N7 [76.7 (3)°]. Le cycle oxazoline, sur lequel sont liés les deux bras éthoxycarbonyles, présente une conformation enveloppe, avec l'atome C3 à 0.5772 (3) Å du plan N4/C14/O1/C2 [r.m.s. déviation 0.046 (3) Å]. Le cycle phényle est porté par l'atome de carbone C14, à la jonction oxazoline–diazépine.

S2. Experimental

Les cristaux ont été obtenus par évaporation à température ambiante d'un mélange (5:5) éther–éthanol (Zhu & Espenson, 1995).

S3. Refinement

Les atomes d'hydrogène ont été positionnés géométriquement et affectés d'un paramètre de déplacement thermique arbitraire (1,3U_eq de l'atome porteur). Cependant, les cartes de densité électronique montrent que les atomes d'hydogène portés par l'atome de carbone C21 ont deux positions d'équilibre avec un degré d'occupation de 0,5 pour chacun.

Computing details

Data collection: KappaCCD Software (Nonius, 1998); data reduction: DENZO and SCALEPAK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: maXus (Mackay et al., 1999); software used to prepare material for publication: maXus.

(II)

Crystal data

C24H25ClN2O6	F(000) = 912
Mr = 472.92	Dx = 1.386 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 9.9783 (3) Å	Cell parameters from 15904 reflections
b = 20.4064 (7) Å	θ = 1–26.1°
c = 11.1476 (3) Å	µ = 0.21 mm^−1
β = 93.231 (2)°	T = 298 K
V = 2266.3 (3) Å^3	Cube, colourless
Z = 4	0.35 × 0.30 × 0.30 mm

Data collection

KappaCCD diffractometer	Rint = 0.031
Radiation source: fine-focus sealed tube	θmax = 26.2°
ϕ scans	h = 0→12
4492 measured reflections	k = 0→25
4379 independent reflections	l = −13→13
3608 reflections with I > 3σ(I)

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: geom, diff
R[F^2 > 2σ(F^2)] = 0.041	H-atom parameters not refined
wR(F^2) = 0.047	Weighting scheme based on measured s.u.'s w = 1/[s^2(Fo^2) + 0.03Fo^2]
S = 1.49	(Δ/σ)max = 0.002
3608 reflections	Δρmax = 0.20 e Å^−3
298 parameters	Δρmin = −0.24 e Å^−3
Primary atom site location: structure-invariant direct methods

Special details

Geometry. All standard uncertainties (except dihedral angles between l.s. planes) are estimated using the full covariance matrix. The standard uncertainties in cell dimensions are are used in calculating the standard uncertainties of bond distances, angles and torsion angles. Angles between l.s. planes have standard uncertainties calculated from atomic positional standard uncertainties; the errors in cell dimensions are not used in this case.

Refinement. Refinement on F²

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
Cl1	0.352530 (12)	0.434476 (5)	−0.008258 (12)	0.06464 (7)
N4	0.70002 (3)	0.234224 (13)	0.27793 (2)	0.02776 (14)
O3	0.47678 (3)	0.167018 (12)	0.47960 (2)	0.04010 (14)
O1	0.48292 (2)	0.261802 (11)	0.31603 (19)	0.03031 (12)
O5	0.62086 (3)	0.389634 (12)	0.34696 (3)	0.04917 (15)
O4	0.83777 (3)	0.372953 (14)	0.31912 (3)	0.05837 (17)
O7	0.87433 (3)	0.143184 (13)	0.09879 (2)	0.04810 (16)
O2	0.64129 (3)	0.210793 (14)	0.59860 (3)	0.05662 (18)
C12	0.46510 (3)	0.329234 (17)	0.10339 (3)	0.03343 (18)
N7	0.69877 (3)	0.198742 (14)	0.01067 (3)	0.03431 (16)
C14	0.56046 (3)	0.232586 (16)	0.22501 (3)	0.02656 (16)
C13	0.54498 (3)	0.273302 (16)	0.10979 (3)	0.02757 (16)
C15	0.50536 (3)	0.163629 (16)	0.20248 (3)	0.02939 (17)
C2	0.56590 (3)	0.269735 (16)	0.42335 (3)	0.03037 (17)
C5	0.80637 (3)	0.242386 (17)	0.19330 (3)	0.03250 (18)
C20	0.37100 (4)	0.158979 (18)	0.16331 (3)	0.0384 (2)
C6	0.79682 (4)	0.189902 (18)	0.09762 (3)	0.03381 (19)
C8	0.61296 (3)	0.255087 (16)	0.00845 (3)	0.03071 (17)
C3	0.70432 (3)	0.281220 (17)	0.37839 (3)	0.03073 (17)
C16	0.57909 (4)	0.106628 (18)	0.22149 (4)	0.0411 (2)
C23	0.47683 (4)	0.108617 (18)	0.55501 (4)	0.0441 (2)
C11	0.45353 (4)	0.364907 (17)	−0.00205 (4)	0.0395 (2)
C22	0.56730 (4)	0.212224 (17)	0.50995 (3)	0.03332 (19)
C19	0.31160 (4)	0.09860 (2)	0.14294 (4)	0.0537 (3)
C9	0.59999 (4)	0.29206 (19)	−0.09581 (3)	0.0422 (2)
C10	0.51943 (4)	0.34683 (2)	−0.10167 (4)	0.0466 (2)
C25	0.73006 (4)	0.352711 (18)	0.34420 (3)	0.0378 (2)
C21	0.68152 (5)	0.15012 (2)	−0.08602 (4)	0.0550 (3)
C18	0.38631 (5)	0.04243 (2)	0.15966 (5)	0.0622 (3)
C26	0.63320 (5)	0.45931 (2)	0.32072 (4)	0.0626 (3)
C27	0.49787 (6)	0.48807 (2)	0.32455 (5)	0.0767 (3)
C17	0.51871 (5)	0.04614 (19)	0.19822 (4)	0.0574 (3)
C24	0.35747 (5)	0.06938 (2)	0.51507 (4)	0.0620 (3)
H12	0.41690	0.34313	0.17099	0.0434*
H2	0.53479	0.30674	0.46725	0.0395*
H5A	0.89227	0.23999	0.23640	0.0422*
H5B	0.79627	0.28459	0.15580	0.0422*
H20	0.31980	0.19848	0.15161	0.0499*
H3	0.77562	0.26932	0.43569	0.0399*
H16	0.67159	0.10903	0.24979	0.0534*
H23A	0.55803	0.08432	0.54571	0.0573*
H23B	0.47193	0.12152	0.63751	0.0573*
H19	0.21860	0.09620	0.11614	0.0698*
H9	0.64629	0.27896	−0.16511	0.0549*
H10	0.50963	0.37203	−0.17437	0.0606*
H21A	0.74592	0.11562	−0.07182	0.0715*	0.50
H21B	0.69562	0.17052	−0.16182	0.0715*	0.50
H21C	0.59252	0.13222	−0.08732	0.0715*	0.50
H18	0.34631	0.00033	0.14356	0.0809*
H26A	0.69460	0.47981	0.37861	0.0814*
H26B	0.66560	0.46441	0.24182	0.0814*
H27A	0.50067	0.53407	0.30675	0.0997*
H27B	0.46687	0.48187	0.40375	0.0997*
H27C	0.43777	0.46657	0.26695	0.0997*
H17	0.57101	0.00704	0.21082	0.0746*
H24A	0.35317	0.03028	0.56247	0.0806*
H24B	0.36397	0.05778	0.43217	0.0806*
H24C	0.27787	0.09498	0.52387	0.0806*
H21D	0.60022	0.16212	−0.1472	0.0715*	0.50
H21E	0.66762	0.10722	−0.03642	0.0715*	0.50
H21F	0.7664	0.1501	−0.1375	0.0715*	0.50

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.06340 (7)	0.04678 (6)	0.08292 (9)	0.01634 (5)	−0.00603 (6)	0.02245 (6)
N4	0.02410 (14)	0.03448 (16)	0.02476 (15)	−0.00016 (12)	0.00348 (12)	0.00033 (12)
O3	0.04684 (16)	0.03791 (15)	0.03547 (14)	−0.01020 (12)	0.00320 (12)	0.00870 (11)
O1	0.02805 (12)	0.03538 (13)	0.02771 (13)	0.00311 (10)	0.00704 (11)	0.00004 (10)
O5	0.04668 (16)	0.03218 (15)	0.06893 (19)	−0.00517 (13)	0.01172 (15)	0.00790 (13)
O4	0.05133 (18)	0.05087 (18)	0.0741 (2)	−0.01888 (14)	0.02862 (16)	−0.00664 (15)
O7	0.04570 (16)	0.04987 (17)	0.04922 (17)	0.01752 (13)	0.01408 (14)	0.00166 (13)
O2	0.06327 (19)	0.0632 (2)	0.04235 (17)	−0.01996 (15)	−0.01196 (16)	0.01675 (14)
C12	0.02987 (19)	0.0326 (2)	0.0377 (2)	−0.00167 (15)	0.00012 (17)	0.00419 (16)
N7	0.03938 (17)	0.03601 (17)	0.02759 (16)	0.00232 (14)	0.00439 (14)	−0.00358 (13)
C14	0.02459 (17)	0.03054 (18)	0.02461 (17)	0.00333 (14)	0.00403 (15)	0.00212 (14)
C13	0.02565 (17)	0.02880 (18)	0.02803 (18)	−0.00242 (14)	−0.00085 (15)	0.00397 (14)
C15	0.03275 (19)	0.03055 (19)	0.02499 (18)	−0.00201 (15)	0.00532 (16)	0.00323 (15)
C2	0.03279 (19)	0.03217 (19)	0.02636 (18)	−0.00281 (15)	0.00697 (16)	−0.00098 (15)
C5	0.02421 (17)	0.0439 (2)	0.02952 (19)	0.00179 (15)	0.00533 (15)	0.00079 (16)
C20	0.0378 (2)	0.0404 (2)	0.0368 (2)	−0.00515 (17)	−0.00182 (18)	0.00490 (17)
C6	0.0329 (2)	0.0380 (2)	0.0309 (2)	0.00135 (17)	0.01115 (17)	0.00194 (16)
C8	0.03150 (18)	0.03291 (19)	0.02756 (18)	−0.00360 (15)	0.00052 (16)	0.00230 (15)
C3	0.03218 (19)	0.0351 (2)	0.02487 (18)	−0.00286 (15)	0.00294 (15)	−0.00120 (15)
C16	0.0399 (2)	0.0341 (2)	0.0494 (2)	0.00169 (17)	0.00992 (19)	0.00541 (18)
C23	0.0493 (2)	0.0350 (2)	0.0484 (2)	−0.00030 (18)	0.0134 (2)	0.01281 (18)
C11	0.0374 (2)	0.0327 (2)	0.0475 (2)	0.00005 (16)	−0.00867 (19)	0.01113 (17)
C22	0.0340 (2)	0.0376 (2)	0.0287 (2)	−0.00209 (16)	0.00877 (18)	−0.00010 (16)
C19	0.0510 (3)	0.0547 (3)	0.0546 (3)	−0.0194 (2)	−0.0057 (2)	0.0017 (2)
C9	0.0510 (2)	0.0489 (2)	0.0266 (2)	−0.00418 (19)	0.00255 (18)	0.00415 (17)
C10	0.0560 (3)	0.0473 (2)	0.0357 (2)	−0.0047 (2)	−0.0076 (2)	0.01607 (19)
C25	0.0430 (2)	0.0403 (2)	0.0305 (2)	−0.00973 (19)	0.00855 (18)	−0.00622 (16)
C21	0.0656 (3)	0.0561 (3)	0.0430 (2)	0.0032 (2)	0.0003 (2)	−0.0181 (2)
C18	0.0752 (3)	0.0392 (3)	0.0723 (3)	−0.0218 (2)	0.0091 (3)	−0.0076 (2)
C26	0.0756 (3)	0.0345 (2)	0.0784 (3)	−0.0090 (2)	0.0195 (3)	0.0075 (2)
C27	0.0939 (4)	0.0404 (3)	0.0955 (4)	0.0065 (3)	0.0063 (3)	0.0010 (3)
C17	0.0684 (3)	0.0301 (2)	0.0743 (3)	0.0040 (2)	0.0198 (3)	0.0021 (2)
C24	0.0744 (3)	0.0478 (3)	0.0638 (3)	−0.0195 (2)	0.0085 (3)	0.0105 (2)

Geometric parameters (Å, º)

N4—C14	1.4818 (4)	C14—C15	1.5264 (5)
N4—C5	1.4686 (4)	C13—C8	1.4003 (4)
N4—C3	1.4732 (4)	C15—C20	1.3896 (5)
O3—C23	1.4584 (4)	C15—C16	1.3862 (5)
O3—C22	1.3216 (4)	C2—C3	1.5139 (5)
O1—C14	1.4394 (4)	C2—C22	1.5192 (5)
O1—C2	1.4253 (4)	C5—C6	1.5107 (5)
O5—C25	1.3265 (4)	C20—C19	1.3805 (5)
O5—C26	1.4582 (5)	C8—C9	1.3856 (5)
O4—C25	1.1990 (4)	C3—C25	1.5331 (5)
O7—C6	1.2272 (4)	C16—C17	1.3915 (6)
O2—C22	1.2001 (4)	C23—C24	1.4825 (6)
C12—C13	1.3916 (4)	C11—C10	1.3726 (5)
C12—C11	1.3819 (5)	C19—C18	1.3743 (6)
N7—C6	1.3500 (5)	C9—C10	1.3761 (6)
N7—C8	1.4329 (4)	C18—C17	1.3681 (6)
N7—C21	1.4680 (5)	C26—C27	1.4752 (7)
C14—C13	1.5303 (4)
C14—N4—C5	116.34 (3)	C15—C20—C19	120.68 (4)
C14—N4—C3	107.69 (2)	O7—C6—N7	122.83 (3)
C5—N4—C3	115.05 (3)	O7—C6—C5	121.91 (3)
C23—O3—C22	116.41 (3)	N7—C6—C5	115.25 (3)
C14—O1—C2	109.20 (2)	N7—C8—C13	121.01 (3)
C25—O5—C26	118.06 (3)	N7—C8—C9	118.61 (3)
C13—C12—C11	119.72 (3)	C13—C8—C9	120.37 (3)
C6—N7—C8	121.85 (3)	N4—C3—C2	99.37 (3)
C6—N7—C21	119.15 (3)	N4—C3—C25	115.37 (3)
C8—N7—C21	118.98 (3)	C2—C3—C25	113.48 (3)
N4—C14—O1	103.91 (2)	C15—C16—C17	119.69 (4)
N4—C14—C13	111.72 (3)	O3—C23—C24	107.10 (3)
N4—C14—C15	114.08 (3)	C12—C11—C10	121.72 (4)
O1—C14—C13	109.51 (3)	O3—C22—O2	125.00 (3)
O1—C14—C15	107.15 (2)	O3—C22—C2	113.26 (3)
C13—C14—C15	110.12 (3)	O2—C22—C2	121.69 (3)
C12—C13—C14	121.25 (3)	C20—C19—C18	119.83 (4)
C12—C13—C8	118.58 (3)	C8—C9—C10	120.58 (3)
C14—C13—C8	120.17 (3)	C11—C10—C9	119.01 (4)
C14—C15—C20	116.54 (3)	O5—C25—O4	123.91 (3)
C14—C15—C16	124.42 (3)	O5—C25—C3	112.67 (3)
C20—C15—C16	119.02 (3)	O4—C25—C3	123.41 (4)
O1—C2—C3	103.73 (2)	C19—C18—C17	120.22 (4)
O1—C2—C22	115.45 (3)	O5—C26—C27	107.12 (3)
C3—C2—C22	110.73 (3)	C16—C17—C18	120.52 (4)
N4—C5—C6	110.74 (3)
C5—N4—C14—O1	−147.75 (3)	O1—C14—C13—C8	179.06 (4)
C5—N4—C14—C13	−29.78 (3)	O1—C14—C15—C20	59.85 (3)
C5—N4—C14—C15	95.92 (3)	O1—C14—C15—C16	−118.39 (4)
C14—N4—C5—C6	−55.51 (3)	C15—C14—C13—C12	117.39 (4)
C3—N4—C14—O1	−16.93 (2)	C13—C14—C15—C20	−59.18 (3)
C3—N4—C14—C13	101.04 (3)	C15—C14—C13—C8	−63.36 (3)
C3—N4—C14—C15	−133.26 (3)	C13—C14—C15—C16	122.58 (4)
C14—N4—C3—C2	34.40 (2)	C12—C13—C8—N7	178.70 (5)
C14—N4—C3—C25	−87.28 (3)	C12—C13—C8—C9	−0.28 (3)
C5—N4—C3—C2	165.93 (3)	C14—C13—C8—N7	−0.57 (3)
C3—N4—C5—C6	177.22 (4)	C14—C13—C8—C9	−179.55 (5)
C5—N4—C3—C25	44.25 (3)	C14—C15—C20—C19	−178.66 (5)
C23—O3—C22—O2	−5.81 (3)	C14—C15—C16—C17	179.85 (6)
C23—O3—C22—C2	176.86 (4)	C16—C15—C20—C19	−0.32 (4)
C22—O3—C23—C24	172.58 (4)	C20—C15—C16—C17	1.66 (4)
C2—O1—C14—N4	−9.45 (2)	O1—C2—C3—N4	−39.33 (2)
C2—O1—C14—C13	−128.94 (3)	O1—C2—C3—C25	83.71 (3)
C2—O1—C14—C15	111.63 (3)	O1—C2—C22—O3	−8.66 (3)
C14—O1—C2—C3	31.29 (2)	O1—C2—C22—O2	173.91 (5)
C14—O1—C2—C22	−90.04 (3)	C22—C2—C3—N4	85.11 (3)
C26—O5—C25—O4	−1.52 (4)	C3—C2—C22—O3	−126.13 (4)
C26—O5—C25—C3	177.66 (5)	C3—C2—C22—O2	56.44 (4)
C25—O5—C26—C27	177.59 (5)	C22—C2—C3—C25	−151.85 (4)
C11—C12—C13—C14	179.91 (5)	N4—C5—C6—O7	−104.27 (4)
C11—C12—C13—C8	0.64 (3)	N4—C5—C6—N7	76.66 (3)
C13—C12—C11—C10	−0.22 (4)	C15—C20—C19—C18	−1.03 (4)
C8—N7—C6—O7	−177.38 (5)	N7—C8—C9—C10	−179.53 (5)
C6—N7—C8—C13	−51.68 (4)	C13—C8—C9—C10	−0.52 (3)
C8—N7—C6—C5	1.69 (3)	N4—C3—C25—O5	106.26 (4)
C6—N7—C8—C9	127.32 (5)	N4—C3—C25—O4	−74.55 (4)
C21—N7—C6—O7	1.12 (3)	C2—C3—C25—O5	−7.47 (3)
C21—N7—C6—C5	−179.81 (5)	C2—C3—C25—O4	171.71 (5)
C21—N7—C8—C13	129.81 (4)	C15—C16—C17—C18	−1.67 (4)
C21—N7—C8—C9	−51.19 (4)	C12—C11—C10—C9	−0.58 (4)
N4—C14—C13—C12	−114.76 (4)	C20—C19—C18—C17	1.04 (4)
N4—C14—C13—C8	64.50 (3)	C8—C9—C10—C11	0.94 (4)
N4—C14—C15—C20	174.28 (4)	C19—C18—C17—C16	0.31 (4)
N4—C14—C15—C16	−3.96 (3)