8-Chloro-6-phenyl-4H-[1,2,4]­triazolo­[4,3-a][1,5]­benzodiazepin-5(6H)-one

The title compound, C₁₆H₁₁ClN₄O, is an anticonvulsant agent. In the crystal, a particularly short C—H...N intermolecular hydrogen bond is noted [H...N 2.22 (2) Å]. The diazepine ring has a boat conformation.

S1. Comment

The title compound, indicated here as RL202,was previously reported to exhibit anticonvulsant activity (Bauer et al., 1974; Fryer et al., 1978). Its crystal structure has been now determined as part of an investigation on the relationships between molecular properties and pharmacological activities of [1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amines with different substitution patterns (Di Braccio et al., 1990; Roma et al., 1991; Grossi et al., 1993).

To our knowledge, the present work reports for the first time the crystal structure of a [1,2,4]triazolo[4,3-a][1,5]benzodiazepinone. The structure of RL202 has been solved by direct methods (Gabe et al., 1989). An ORTEPII view (Johnson, 1976) is shown in Fig. 1. The diazepine ring has a boat conformation; the asymmetry parameters (PARST; Nardelli, 1983, 1995) give evidence of a pseudo mirror plane passing through C4 [ΔC_s = 0.0420 (4)]. The extent of the boat conformation can be described in terms of the (acute) dihedral angles between the central plane, defined by atoms N11, C3a, C5, N6 and the 'bow' and 'stern' planes, defined by atoms C3a, C4, C5 and C6a, C10a, N11, N6, respectively (Hamor & Martin, 1983). The bow and stern angles in RL202 [55.1 (1) and 37.1 (1)°] compare well with analogous values obtained for [1,2,4]triazolo[4,3-a][1,4]benzodiazepines, where the ranges for bow-angles and stern-angles are 53.4–55.5 and 31.2–36.2°, respectively (Hamor & Martin, 1983). For Clobazam, an important 1,5-benzodiazepinedione (Butcher & Hamor, 1985), the corresponding values are 59.4 (5) and 40.7 (5)°, respectively.

The main conformational parameter of RL202 is the torsion angle of the non-condensed phenyl ring. Its rather high value, 57.3 (2)° for the C6a—N6—C1'-C6' torsion angle, can be referred back to the steric hindrance with neighbouring atoms [C2'···O 2.929 (2), C6'···C7 3.300 (2) Å]. In order to investigate the effects of packing forces on the observed conformation, the geometry of the isolated molecule has been calculated with ab initio molecular orbital methods at the HF/6–31 G^* level (Hariharan & Pople, 1973;full optimization, 356 basis functions). In this case, the internal strain relaxes through an even larger torsion angle of the phenyl ring (68.4°); the two non-bonded distances become 2.97 and 3.53 Å, respectively.

Intermolecular contacts in the crystal state correspond to van der Waals interactions, with the exception of a stronger C—H···N hydrogen bond [C1—H1 1.00 (2) Å, C1···N3 3.191 (2) Å, H1···N3 2.22 (2) Å, C1—H1···N3 163.7(1.5)°, N3 in x, 3/2 − y, −1/2 + z] and of a weaker C—H···O interaction [C6'-H6' 0.94 (2) Å, C6'···O 3.371 (2) Å, H6'···O 2.45 (2) Å, C6'-H6'···O 166.5(1.7)°, O in x, 3/2 − y, −1/2 + z]. According to a recent review on C—H···N hydrogen bonds (Mascal, 1998), the present H···N distance locates on the short side of the distribution.

Atomic charges have been evaluated for the experimental molecule with re-normalized C—H bond distances; the calculations have been performed at the HF/6–31 G^* level with the method of the best-fit to the electrostatic potential. The resulting values for exposed heteroatoms in the molecule (O −0.59, N3 − 0.39, N2 − 0.34, Cl −0.13 a.u.), along with the packing geometry, support the observed interactions. Charges calculated for H1 and H6' are 0.14 and 0.17 a.u., respectively.

S2. Experimental

Compound RL202 was crystallized from methanol.

S3. Refinement

In the final least-squares cycles zero weight was given to four low-angle reflections, as affected by extinction or experimental error. All the hydrogen atoms were localized from difference syntheses and refined isotropically. The range of resulting C—H bond lengths is 0.92 to 1.01 A with a nearly constant su of 0.02 A. No correlation matrix elements larger than 0.50 were found.

The sequence of programs used to generate CIF:

SHELXL97 -> PREP97 (by Professor M. Nardelli) -> PARST97 -> PARSTCIF

Computing details

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: NRCVAX (Gabe et al., 1989) and CADABS (local software); program(s) used to solve structure: NRCVAX; program(s) used to refine structure: NRCVAX and SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP (Johnson, 1976); software used to prepare material for publication: PARST (Nardelli, 1983, 1995) and PARSTCIF (Nardelli, 1991).

Figures

Fig. 1. A molecule of RL202 with numbering scheme of atoms. Displacement ellipsoids are drawn at 0.50 level of probability. H atoms are on an arbitrary scale.

8-Chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one

Crystal data

C16H11ClN4O	Dx = 1.442 Mg m^−3 Dm = 1.441 Mg m^−3 Dm measured by floating crystals method
Mr = 310.74	Melting point: 571 K
Monoclinic, P21/c	Mo Kα radiation, λ = 0.7107 Å
a = 16.983 (4) Å	Cell parameters from 25 reflections
b = 8.863 (2) Å	θ = 16.5–19.7°
c = 9.784 (4) Å	µ = 0.27 mm^−1
β = 103.67 (3)°	T = 293 K
V = 1431.0 (8) Å^3	Prism, colourless
Z = 4	0.54 × 0.46 × 0.40 mm
F(000) = 640.0

Data collection

Enraf-Nonius CAD-4 diffractometer	3462 reflections with Fo > 4 σ(Fo)
Radiation source: X-ray	Rint = 0.000
Graphite monochromator	θmax = 29.9°, θmin = 2.6°
ω–θ scan mode	h = 0→23
Absorption correction: ψ scan (North et al., 1968)	k = 0→12
Tmin = 0.823, Tmax = 0.896	l = −13→13
4161 measured reflections	2 standard reflections every 90 min
4161 independent reflections	intensity decay: 5%

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.040	Hydrogen site location: difference Fourier map
wR(F^2) = 0.110	All H-atom parameters refined
S = 1.04	Calculated w = 1/[σ^2(Fo^2) + (0.0524P)^2 + 0.3463P] where P = (Fo^2 + 2Fc^2)/3
4157 reflections	(Δ/σ)max = 0.001
243 parameters	Δρmax = 0.26 e Å^−3
0 restraints	Δρmin = −0.36 e Å^−3
0 constraints

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

	x	y	z	Uiso*/Ueq
C1	0.96531 (8)	0.7749 (2)	0.6615 (1)	0.0436 (4)
N2	1.01163 (7)	0.7650 (2)	0.7882 (1)	0.0483 (4)
N3	0.98292 (7)	0.8695 (1)	0.8715 (1)	0.0421 (3)
C3a	0.92086 (7)	0.9369 (2)	0.7909 (1)	0.0338 (3)
C4	0.86656 (7)	1.0520 (2)	0.8289 (1)	0.0371 (4)
C5	0.78386 (7)	0.9816 (2)	0.8141 (1)	0.0374 (4)
N6	0.74182 (6)	0.9478 (1)	0.6784 (1)	0.0332 (3)
C6a	0.77051 (7)	0.9776 (1)	0.5549 (1)	0.0309 (3)
C7	0.71696 (7)	1.0427 (2)	0.4396 (1)	0.0356 (4)
C8	0.74001 (8)	1.0633 (2)	0.3151 (1)	0.0379 (4)
C9	0.81573 (9)	1.0198 (2)	0.2989 (1)	0.0438 (4)
C10	0.86979 (8)	0.9598 (2)	0.4138 (1)	0.0416 (4)
C10a	0.84801 (7)	0.9384 (2)	0.5407 (1)	0.0331 (3)
N11	0.90638 (6)	0.8807 (1)	0.6571 (1)	0.0348 (3)
Cl	0.67268 (2)	1.14899 (5)	0.17568 (4)	0.0556 (1)
O	0.75713 (7)	0.9534 (2)	0.9154 (1)	0.0619 (4)
C1'	0.66060 (7)	0.8872 (1)	0.6559 (1)	0.0336 (3)
C2'	0.60226 (8)	0.9632 (2)	0.7060 (2)	0.0460 (4)
C3'	0.52425 (9)	0.9055 (2)	0.6817 (2)	0.0531 (5)
C4'	0.50528 (8)	0.7728 (2)	0.6079 (2)	0.0514 (5)
C5'	0.5636 (1)	0.6987 (2)	0.5570 (2)	0.0545 (5)
C6'	0.64216 (9)	0.7548 (2)	0.5817 (2)	0.0452 (5)
H1	0.9677 (10)	0.711 (2)	0.5781 (19)	0.052 (5)*
H41	0.8627 (10)	1.1417 (19)	0.7644 (18)	0.043 (4)*
H42	0.8872 (10)	1.083 (2)	0.9237 (19)	0.051 (5)*
H7	0.6646 (10)	1.073 (2)	0.4493 (18)	0.047 (4)*
H9	0.8325 (10)	1.034 (2)	0.2145 (19)	0.053 (5)*
H10	0.9219 (11)	0.936 (2)	0.4080 (18)	0.051 (5)*
H2'	0.6144 (12)	1.058 (2)	0.756 (2)	0.064 (6)*
H3'	0.4814 (13)	0.962 (3)	0.717 (2)	0.082 (7)*
H4'	0.4493 (12)	0.732 (2)	0.589 (2)	0.067 (6)*
H5'	0.5508 (13)	0.606 (3)	0.503 (2)	0.076 (6)*
H6'	0.6817 (12)	0.702 (2)	0.548 (2)	0.062 (5)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0367 (6)	0.0607 (8)	0.0339 (6)	0.0141 (6)	0.0090 (5)	0.0001 (6)
N2	0.0412 (6)	0.0667 (8)	0.0354 (6)	0.0145 (6)	0.0061 (5)	0.0019 (5)
N3	0.0356 (5)	0.0570 (7)	0.0322 (5)	0.0017 (5)	0.0051 (4)	−0.0006 (5)
C3a	0.0293 (5)	0.0436 (6)	0.0294 (5)	−0.0045 (5)	0.0084 (4)	−0.0017 (5)
C4	0.0316 (5)	0.0437 (7)	0.0366 (6)	−0.0057 (5)	0.0091 (5)	−0.0090 (5)
C5	0.0332 (6)	0.0485 (7)	0.0328 (6)	−0.0051 (5)	0.0124 (5)	−0.0054 (5)
N6	0.0271 (4)	0.0439 (5)	0.0310 (5)	−0.0051 (4)	0.0116 (3)	−0.0028 (4)
C6a	0.0280 (5)	0.0363 (6)	0.0299 (5)	−0.0016 (4)	0.0099 (4)	−0.0009 (4)
C7	0.0299 (5)	0.0395 (6)	0.0376 (6)	0.0031 (5)	0.0083 (4)	0.0007 (5)
C8	0.0391 (6)	0.0391 (6)	0.0337 (6)	0.0038 (5)	0.0050 (5)	0.0055 (5)
C9	0.0444 (7)	0.0572 (8)	0.0325 (6)	0.0045 (6)	0.0147 (5)	0.0084 (6)
C10	0.0333 (6)	0.0595 (8)	0.0352 (6)	0.0063 (6)	0.0147 (5)	0.0052 (6)
C10a	0.0284 (5)	0.0424 (6)	0.0289 (5)	0.0013 (4)	0.0079 (4)	0.0013 (4)
N11	0.0287 (4)	0.0484 (6)	0.0276 (4)	0.0045 (4)	0.0072 (3)	0.0003 (4)
Cl	0.0591 (2)	0.0595 (2)	0.0436 (2)	0.0153 (2)	0.0027 (2)	0.0158 (2)
O	0.0516 (6)	0.1032 (10)	0.0357 (5)	−0.0235 (6)	0.0201 (4)	−0.0079 (6)
C1'	0.0275 (5)	0.0391 (6)	0.0356 (6)	−0.0043 (4)	0.0105 (4)	−0.0002 (5)
C2'	0.0357 (6)	0.0505 (8)	0.0562 (8)	−0.0054 (6)	0.0197 (6)	−0.0127 (6)
C3'	0.0317 (6)	0.0696 (10)	0.0622 (9)	−0.0031 (6)	0.0194 (6)	−0.0046 (8)
C4'	0.0329 (6)	0.0636 (9)	0.0561 (8)	−0.0137 (6)	0.0074 (6)	0.0047 (7)
C5'	0.0488 (8)	0.0487 (8)	0.0645 (10)	−0.0161 (7)	0.0101 (7)	−0.0105 (7)
C6'	0.0390 (6)	0.0433 (7)	0.0554 (8)	−0.0045 (6)	0.0151 (6)	−0.0093 (6)

Geometric parameters (Å, º)

C1—N2	1.304 (2)	C8—C9	1.387 (2)
C1—N11	1.365 (2)	C8—Cl	1.734 (1)
C1—H1	1.00 (1)	C9—C10	1.379 (2)
N2—N3	1.395 (2)	C9—H9	0.94 (2)
N3—C3a	1.302 (2)	C10—C10a	1.390 (2)
C3a—C4	1.480 (2)	C10—H10	0.92 (1)
C3a—N11	1.367 (2)	C10a—N11	1.417 (2)
C4—C5	1.512 (2)	C1'—C2'	1.380 (2)
C4—H41	1.01 (1)	C1'—C6'	1.376 (2)
C4—H42	0.95 (1)	C2'—C3'	1.387 (2)
C5—N6	1.383 (2)	C2'—H2'	0.97 (2)
C5—O	1.210 (2)	C3'—C4'	1.378 (3)
N6—C6a	1.430 (2)	C3'—H3'	1.01 (2)
N6—C1'	1.448 (2)	C4'—C5'	1.376 (3)
C6a—C7	1.395 (2)	C4'—H4'	0.99 (2)
C6a—C10a	1.400 (2)	C5'—C6'	1.390 (2)
C7—C8	1.377 (2)	C5'—H5'	0.98 (2)
C7—H7	0.96 (1)	C6'—H6'	0.94 (2)
N2—C1—N11	110.4 (1)	C8—C9—H9	123 (1)
N2—C1—H1	127 (1)	C10—C9—H9	119 (1)
N11—C1—H1	122 (1)	C9—C10—C10a	121.0 (1)
C1—N2—N3	107.2 (1)	C9—C10—H10	120 (1)
N2—N3—C3a	107.2 (1)	C10a—C10—H10	119 (1)
N3—C3a—C4	128.8 (1)	C6a—C10a—C10	120.7 (1)
N3—C3a—N11	110.4 (1)	C6a—C10a—N11	120.3 (1)
C4—C3a—N11	120.6 (1)	C10—C10a—N11	119.0 (1)
C3a—C4—C5	108.1 (1)	C1—N11—C3a	104.8 (1)
C3a—C4—H41	110 (1)	C1—N11—C10a	129.9 (1)
C3a—C4—H42	110 (1)	C3a—N11—C10a	124.9 (1)
C5—C4—H41	110 (1)	N6—C1'—C2'	120.2 (1)
C5—C4—H42	109 (1)	N6—C1'—C6'	119.1 (1)
H41—C4—H42	110 (1)	C2'—C1'—C6'	120.7 (1)
C4—C5—N6	116.0 (1)	C1'—C2'—C3'	119.7 (1)
C4—C5—O	121.8 (1)	C1'—C2'—H2'	121 (1)
N6—C5—O	122.2 (1)	C3'—C2'—H2'	119 (1)
C5—N6—C6a	124.7 (1)	C2'—C3'—C4'	120.0 (2)
C5—N6—C1'	118.9 (1)	C2'—C3'—H3'	120 (1)
C6a—N6—C1'	116.3 (1)	C4'—C3'—H3'	120 (1)
N6—C6a—C7	118.2 (1)	C3'—C4'—C5'	119.9 (2)
N6—C6a—C10a	123.7 (1)	C3'—C4'—H4'	120 (1)
C7—C6a—C10a	118.1 (1)	C5'—C4'—H4'	120 (1)
C6a—C7—C8	120.2 (1)	C4'—C5'—C6'	120.7 (2)
C6a—C7—H7	119 (1)	C4'—C5'—H5'	121 (1)
C8—C7—H7	121 (1)	C6'—C5'—H5'	119 (1)
C7—C8—C9	122.0 (1)	C1'—C6'—C5'	119.1 (1)
C7—C8—Cl	118.8 (1)	C1'—C6'—H6'	121 (1)
C9—C8—Cl	119.2 (1)	C5'—C6'—H6'	120 (1)
C8—C9—C10	118.1 (1)
N11—C1—N2—N3	−0.5 (2)	C6a—C7—C8—C9	0.6 (2)
H1—C1—N2—N3	−175 (1)	C6a—C7—C8—Cl	−178.4 (1)
N2—C1—N11—C3a	0.9 (2)	H7—C7—C8—C9	−179 (1)
N2—C1—N11—C10a	173.6 (1)	H7—C7—C8—Cl	1 (1)
H1—C1—N11—C3a	177 (1)	C7—C8—C9—C10	−2.6 (2)
H1—C1—N11—C10a	−10 (1)	C7—C8—C9—H9	−179 (1)
C1—N2—N3—C3a	0.0 (2)	Cl—C8—C9—C10	176.4 (1)
N2—N3—C3a—C4	177.0 (1)	Cl—C8—C9—H9	0 (1)
N2—N3—C3a—N11	0.5 (2)	C8—C9—C10—C10a	2.3 (2)
N3—C3a—C4—C5	−111.7 (2)	C8—C9—C10—H10	−175 (1)
N3—C3a—C4—H41	128 (1)	H9—C9—C10—C10a	179 (1)
N3—C3a—C4—H42	8 (1)	H9—C9—C10—H10	1 (2)
N11—C3a—C4—C5	64.4 (2)	C9—C10—C10a—C6a	−0.1 (2)
N11—C3a—C4—H41	−55 (1)	C9—C10—C10a—N11	−178.1 (1)
N11—C3a—C4—H42	−175 (1)	H10—C10—C10a—C6a	178 (1)
N3—C3a—N11—C1	−0.9 (2)	H10—C10—C10a—N11	0 (1)
N3—C3a—N11—C10a	−174.0 (1)	C6a—C10a—N11—C1	145.1 (1)
C4—C3a—N11—C1	−177.6 (1)	C6a—C10a—N11—C3a	−43.5 (2)
C4—C3a—N11—C10a	9.2 (2)	C10—C10a—N11—C1	−36.9 (2)
C3a—C4—C5—N6	−68.3 (1)	C10—C10a—N11—C3a	134.5 (1)
C3a—C4—C5—O	110.0 (2)	N6—C1'—C2'—C3'	178.9 (1)
H41—C4—C5—N6	52 (1)	N6—C1'—C2'—H2'	0 (1)
H41—C4—C5—O	−129 (1)	C6'—C1'—C2'—C3'	0.3 (2)
H42—C4—C5—N6	172 (1)	C6'—C1'—C2'—H2'	−177 (1)
H42—C4—C5—O	−9 (1)	N6—C1'—C6'—C5'	−178.4 (1)
C4—C5—N6—C6a	−1.4 (2)	N6—C1'—C6'—H6'	2 (1)
C4—C5—N6—C1'	−176.9 (1)	C2'—C1'—C6'—C5'	0.3 (2)
O—C5—N6—C6a	−179.6 (1)	C2'—C1'—C6'—H6'	−179 (1)
O—C5—N6—C1'	4.8 (2)	C1'—C2'—C3'—C4'	0.0 (3)
C5—N6—C6a—C7	−134.4 (1)	C1'—C2'—C3'—H3'	−178 (2)
C5—N6—C6a—C10a	48.9 (2)	H2'—C2'—C3'—C4'	179 (1)
C1'—N6—C6a—C7	41.3 (2)	H2'—C2'—C3'—H3'	0 (2)
C1'—N6—C6a—C10a	−135.4 (1)	C2'—C3'—C4'—C5'	−0.7 (3)
C5—N6—C1'—C2'	54.6 (2)	C2'—C3'—C4'—H4'	−178 (1)
C5—N6—C1'—C6'	−126.8 (1)	H3'—C3'—C4'—C5'	179 (2)
C6a—N6—C1'—C2'	−121.3 (1)	H3'—C3'—C4'—H4'	0 (2)
C6a—N6—C1'—C6'	57.3 (2)	C3'—C4'—C5'—C6'	1.2 (3)
N6—C6a—C7—C8	−175.3 (1)	C3'—C4'—C5'—H5'	−178 (2)
N6—C6a—C7—H7	5 (1)	H4'—C4'—C5'—C6'	180 (1)
C10a—C6a—C7—C8	1.6 (2)	H4'—C4'—C5'—H5'	0 (2)
C10a—C6a—C7—H7	−177 (1)	C4'—C5'—C6'—C1'	−1.0 (3)
N6—C6a—C10a—C10	174.8 (1)	C4'—C5'—C6'—H6'	179 (1)
N6—C6a—C10a—N11	−7.2 (2)	H5'—C5'—C6'—C1'	179 (2)
C7—C6a—C10a—C10	−1.9 (2)	H5'—C5'—C6'—H6'	0 (2)
C7—C6a—C10a—N11	176.1 (1)