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Acta Cryst. (2009). E65, o2363-o2364    [ doi:10.1107/S1600536809034837 ]

2,2,4-Trimethyl-5-(4-tolylsulfonyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

K. Ravichandran, K. Sathiyaraj, S. S. Ilango, S. Ponnuswamy and M. N. Ponnuswamy

Abstract top

In the title compound, C19H24N2O2S, the benzodiazepine ring adopts a distorted boat conformation. The S atom shows a distorted tetrahedral geometry, with the O-S-O [119.16 (14)°] and N-S-C [107.48 (10)°] angles deviating significantly from ideal values. The crystal packing is controlled by C-H...O, N-H...O and C-H...[pi] interactions.

Comment top

Benzodiazepines are known for their natural occurrence in filamentous fungi and actinomycetes of the genera pencillium, aspergillus and streptomyces. Benzodiazepines from aspergillus include asperlicin, which is used for treatment of gastrointestinal and central nervous system (CNS) disorders (Rahbaek et al., 1999). In view of these importance and to ascertain the molecular conformation, a crystallographic study of the title compound has been carried out.

The ORTEP diagram of the title compound is shown in Fig.1. The benzodiazepine ring adopts a distorted boat conformation. The puckering parameters (Cremer & Pople, 1975) and the asymmetry parameters (Nardelli, 1983) for this ring are q2 = 0.976 (3) Å, q3 = 0.068 (3) Å, φ2 = 152.5 (2)°, φ3 = 30.0 (1)° and Δ2(C4)=7.8 (1)°. Atom S takes up a distorted tetrahedral geometry, with the O—S—O and N—S—C angles deviating significantly from ideal values, and this may be attributed to the Thorpe-Ingold effect (Bassindale, 1984). The sum of the bond angles at N1 (342.9°) of the benzodiazepine ring is in accordance with sp3 hybridization, whereas the one at N5(359.7°) is in sp2 hybridization, respectively.

The crystal packing is controlled by C—H···O, N—H···O and C—H···π types of intra and intermolecular interactions. Atom N1 at (x, y, z) donates a proton to O1 (-x, y + 1/2, -z + 1/2 + 1), which forms a one-dimesional C7 chain (Bernstein et al., 1995) running along b–axis. The intermolecular hydrogen bond C14—H14B···O1 connects the molecule into a C6 one dimensional chain running along a–axis as shown in Fig 2. The methyl group H atom in the benzodiazepine ring interacts with the centroid atom of the toluenesulfonyl ring through an intramolecular C—H···π interaction involving atom C13, the separation between H13A and the centroid (Cg2) of the ring (C15/C16/C17/C18/C19/C20) being 2.899 Å.

Related literature top

For the use of benzodiazepines in the treatment of gastrointestinal and central nervous system disorders, see: Rahbaek et al. (1999). For hydrogen-bond motifs, see: Bernstein et al. (1995). For puckering and asymmetry parameters, see: Cremer & Pople (1975); ); Nardelli (1983). For the Thorpe-Ingold effect, see: Bassindale (1984). For details of the preparation, see: Ponnuswamy et al. (2006). Cg2 is the centroid of the = C15–C20 ring.

Experimental top

To a solution of 2,2,4-Trimethyl-1H-tetrahydro-1,5-benzodiazepine (0.59 g) in anhydrous benzene (16 ml), triethylamine (0.7 ml) and 4-toluenesulfonyl chloride (1 gm) were added. The reaction mixture was allowed to reflux for 16 hrs. The benzene solution was washed with water, dried over anhydrous Na2SO4 and concentrated. The resulting mass was purified by crystallization from benzene (Ponnuswamy et al., 2006).

Refinement top

The amino H atom was freely refined. The other H atoms were positioned geometrically (C—H=0.93–0.98 Å) and allowed to ride on their parent atoms, with 1.5Ueq(Cmethyl) or 1.2 Ueq(C). PLATON (Spek, 2009) detected a solvent accessible void of approximately 31 Å3. This void could have initially contained solvent molecules but these molecules have since evaporated from the structure without degradation of the crystal.

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. Perspective view of the molecule showing the displacement ellipsoids at 30% probability level. H atoms have been omitted for clarity.
[Figure 2] Fig. 2. The crystal packing of the molecules viewed down c–axis. H atoms not involved in hydrogen bonding have been omitted for clarity.
2,2,4-Trimethyl-5-(4-tolylsulfonyl)-2,3,4,5-tetrahydro-1H- 1,5-benzodiazepine top
Crystal data top
C19H24N2O2SF(000) = 736
Mr = 344.46Dx = 1.202 Mg m−3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 2546 reflections
a = 7.3658 (3) Åθ = 1.8–29.4°
b = 14.8013 (8) ŵ = 0.18 mm−1
c = 17.4556 (10) ÅT = 293 K
V = 1903.07 (17) Å3Block, colourless
Z = 40.25 × 0.20 × 0.20 mm
Data collection top
Bruker Kappa APEXII area-detector
diffractometer		5154 independent reflections
Radiation source: fine-focus sealed tube3278 reflections with I > 2σ(I)
graphiteRint = 0.034
ω and φ scansθmax = 29.4°, θmin = 1.8°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2001)		h = −5→10
Tmin = 0.957, Tmax = 0.964k = −20→18
13544 measured reflectionsl = −23→23
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.047H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.145 w = 1/[σ2(Fo2) + (0.0742P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.009
5154 reflectionsΔρmax = 0.18 e Å−3
224 parametersΔρmin = −0.19 e Å−3
0 restraintsAbsolute structure: Flack (1983), 2171 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: −0.12 (9)
Crystal data top
C19H24N2O2SV = 1903.07 (17) Å3
Mr = 344.46Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 7.3658 (3) ŵ = 0.18 mm−1
b = 14.8013 (8) ÅT = 293 K
c = 17.4556 (10) Å0.25 × 0.20 × 0.20 mm
Data collection top
Bruker Kappa APEXII area-detector
diffractometer		5154 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2001)		3278 reflections with I > 2σ(I)
Tmin = 0.957, Tmax = 0.964Rint = 0.034
13544 measured reflectionsθmax = 29.4°
Refinement top
R[F2 > 2σ(F2)] = 0.047H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.145Δρmax = 0.18 e Å−3
S = 1.04Δρmin = −0.19 e Å−3
5154 reflectionsAbsolute structure: Flack (1983), 2171 Friedel pairs
224 parametersFlack parameter: −0.12 (9)
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
xyzUiso*/Ueq
S10.08799 (9)0.63541 (4)0.80960 (4)0.0620 (2)
O10.2717 (3)0.63113 (17)0.78264 (12)0.0849 (6)
O20.0096 (3)0.55749 (13)0.84498 (12)0.0870 (7)
N1−0.0887 (3)0.84795 (14)0.70370 (13)0.0566 (5)
H1−0.072 (4)0.897 (2)0.6945 (18)0.073 (9)*
C2−0.2833 (3)0.83013 (16)0.71790 (15)0.0520 (6)
C3−0.3323 (3)0.73221 (16)0.70025 (16)0.0577 (6)
H3A−0.46230.72570.70740.069*
H3B−0.30780.72180.64640.069*
C4−0.2402 (3)0.65759 (15)0.74511 (17)0.0589 (7)
H4−0.27190.66420.79930.071*
N5−0.0387 (3)0.66325 (13)0.73728 (11)0.0524 (5)
C60.0396 (3)0.70241 (16)0.66986 (13)0.0497 (6)
C70.1455 (3)0.6493 (2)0.62250 (16)0.0659 (7)
H70.15650.58770.63200.079*
C80.2354 (4)0.6879 (3)0.56082 (18)0.0855 (10)
H80.30700.65240.52890.103*
C90.2182 (4)0.7779 (3)0.54737 (17)0.0862 (11)
H90.28190.80410.50710.103*
C100.1077 (4)0.8310 (2)0.59246 (15)0.0676 (7)
H100.09540.89220.58140.081*
C110.0141 (3)0.79417 (17)0.65442 (13)0.0501 (6)
C12−0.3967 (5)0.8894 (2)0.6654 (2)0.0813 (9)
H12A−0.37350.95180.67670.122*
H12B−0.52310.87660.67320.122*
H12C−0.36520.87730.61300.122*
C13−0.3238 (4)0.8554 (2)0.80092 (17)0.0704 (7)
H13A−0.25260.81820.83450.106*
H13B−0.45040.84600.81130.106*
H13C−0.29390.91770.80920.106*
C14−0.3082 (5)0.5663 (2)0.7171 (3)0.0999 (13)
H14A−0.28210.56000.66350.150*
H14B−0.43690.56230.72510.150*
H14C−0.24850.51900.74510.150*
C150.0750 (3)0.72366 (16)0.87704 (14)0.0516 (5)
C160.1482 (4)0.80712 (19)0.85876 (15)0.0640 (7)
H160.20350.81650.81150.077*
C170.1378 (4)0.8753 (2)0.91126 (17)0.0759 (8)
H170.18730.93130.89880.091*
C180.0569 (4)0.8647 (2)0.98198 (17)0.0722 (7)
C19−0.0125 (4)0.7808 (2)0.99895 (18)0.0796 (9)
H19−0.06660.77121.04640.095*
C20−0.0035 (4)0.7106 (2)0.94719 (17)0.0700 (8)
H20−0.05080.65430.96000.084*
C210.0455 (7)0.9425 (3)1.0377 (2)0.1170 (14)
H21A−0.01470.92291.08360.176*
H21B−0.02170.99111.01500.176*
H21C0.16570.96281.05010.176*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0663 (4)0.0509 (3)0.0687 (4)0.0183 (3)0.0157 (3)0.0095 (3)
O10.0646 (11)0.1087 (16)0.0812 (13)0.0422 (12)0.0166 (10)0.0088 (13)
O20.1298 (19)0.0453 (10)0.0858 (13)0.0116 (11)0.0213 (13)0.0147 (10)
N10.0579 (12)0.0403 (11)0.0715 (13)−0.0081 (9)0.0017 (11)−0.0036 (10)
C20.0474 (12)0.0439 (12)0.0648 (15)0.0013 (9)−0.0032 (11)−0.0035 (11)
C30.0432 (11)0.0530 (13)0.0770 (17)−0.0057 (10)0.0066 (12)−0.0146 (13)
C40.0530 (13)0.0434 (13)0.0803 (17)−0.0027 (11)0.0239 (13)−0.0049 (12)
N50.0497 (11)0.0486 (11)0.0591 (11)0.0025 (8)0.0130 (9)−0.0015 (9)
C60.0443 (12)0.0558 (13)0.0491 (12)−0.0020 (10)0.0070 (10)−0.0089 (10)
C70.0542 (14)0.0773 (19)0.0663 (15)0.0042 (13)0.0106 (12)−0.0189 (15)
C80.0705 (19)0.128 (3)0.0583 (18)−0.001 (2)0.0171 (16)−0.0234 (19)
C90.0677 (19)0.140 (4)0.0504 (16)−0.031 (2)0.0072 (14)0.005 (2)
C100.0623 (16)0.087 (2)0.0541 (14)−0.0195 (15)−0.0074 (13)0.0098 (14)
C110.0442 (11)0.0583 (14)0.0478 (12)−0.0100 (10)−0.0031 (10)−0.0029 (11)
C120.081 (2)0.0666 (17)0.097 (2)0.0052 (16)−0.0252 (18)0.0046 (16)
C130.0620 (15)0.0673 (17)0.0819 (18)0.0051 (13)0.0077 (14)−0.0183 (16)
C140.077 (2)0.0482 (15)0.174 (4)−0.0146 (14)0.024 (2)−0.018 (2)
C150.0412 (11)0.0547 (13)0.0590 (13)0.0080 (10)0.0036 (11)0.0126 (11)
C160.0731 (17)0.0651 (17)0.0538 (14)−0.0065 (14)−0.0021 (13)0.0170 (13)
C170.091 (2)0.0607 (17)0.0764 (19)−0.0149 (15)−0.0173 (16)0.0148 (15)
C180.0755 (18)0.0681 (18)0.0730 (17)0.0079 (16)−0.0034 (15)−0.0024 (16)
C190.079 (2)0.092 (2)0.0674 (17)0.0025 (17)0.0194 (16)−0.0025 (17)
C200.0712 (17)0.0671 (18)0.0717 (17)−0.0057 (14)0.0213 (15)0.0072 (14)
C210.144 (4)0.103 (3)0.104 (3)0.019 (3)−0.017 (3)−0.032 (2)
Geometric parameters (Å, °) top
S1—O21.430 (2)C10—C111.394 (3)
S1—O11.434 (2)C10—H100.9300
S1—N51.623 (2)C12—H12A0.9600
S1—C151.761 (3)C12—H12B0.9600
N1—C111.395 (3)C12—H12C0.9600
N1—C21.478 (3)C13—H13A0.9600
N1—H10.75 (3)C13—H13B0.9600
C2—C121.519 (4)C13—H13C0.9600
C2—C131.526 (4)C14—H14A0.9600
C2—C31.525 (3)C14—H14B0.9600
C3—C41.515 (4)C14—H14C0.9600
C3—H3A0.9700C15—C201.368 (4)
C3—H3B0.9700C15—C161.385 (4)
C4—N51.493 (3)C16—C171.366 (4)
C4—C141.522 (4)C16—H160.9300
C4—H40.9800C17—C181.380 (4)
N5—C61.433 (3)C17—H170.9300
C6—C71.382 (3)C18—C191.375 (4)
C6—C111.397 (3)C18—C211.510 (5)
C7—C81.387 (5)C19—C201.379 (4)
C7—H70.9300C19—H190.9300
C8—C91.359 (5)C20—H200.9300
C8—H80.9300C21—H21A0.9600
C9—C101.378 (5)C21—H21B0.9600
C9—H90.9300C21—H21C0.9600
O2—S1—O1119.16 (14)N1—C11—C10121.6 (2)
O2—S1—N5107.96 (13)N1—C11—C6120.6 (2)
O1—S1—N5107.36 (11)C10—C11—C6117.6 (2)
O2—S1—C15106.71 (12)C2—C12—H12A109.5
O1—S1—C15107.67 (14)C2—C12—H12B109.5
N5—S1—C15107.48 (10)H12A—C12—H12B109.5
C11—N1—C2121.86 (19)C2—C12—H12C109.5
C11—N1—H1109 (2)H12A—C12—H12C109.5
C2—N1—H1112 (3)H12B—C12—H12C109.5
N1—C2—C12109.2 (2)C2—C13—H13A109.5
N1—C2—C13107.8 (2)C2—C13—H13B109.5
C12—C2—C13108.9 (2)H13A—C13—H13B109.5
N1—C2—C3111.42 (19)C2—C13—H13C109.5
C12—C2—C3107.3 (2)H13A—C13—H13C109.5
C13—C2—C3112.2 (2)H13B—C13—H13C109.5
C4—C3—C2118.8 (2)C4—C14—H14A109.5
C4—C3—H3A107.6C4—C14—H14B109.5
C2—C3—H3A107.6H14A—C14—H14B109.5
C4—C3—H3B107.6C4—C14—H14C109.5
C2—C3—H3B107.6H14A—C14—H14C109.5
H3A—C3—H3B107.0H14B—C14—H14C109.5
N5—C4—C3110.93 (19)C20—C15—C16119.8 (3)
N5—C4—C14110.3 (2)C20—C15—S1121.1 (2)
C3—C4—C14109.5 (3)C16—C15—S1119.09 (19)
N5—C4—H4108.7C17—C16—C15118.9 (3)
C3—C4—H4108.7C17—C16—H16120.6
C14—C4—H4108.7C15—C16—H16120.6
C6—N5—C4119.9 (2)C16—C17—C18122.7 (3)
C6—N5—S1120.68 (16)C16—C17—H17118.7
C4—N5—S1119.08 (17)C18—C17—H17118.7
C7—C6—C11120.9 (2)C19—C18—C17117.2 (3)
C7—C6—N5119.2 (2)C19—C18—C21121.9 (3)
C11—C6—N5119.8 (2)C17—C18—C21120.9 (3)
C6—C7—C8120.0 (3)C18—C19—C20121.5 (3)
C6—C7—H7120.0C18—C19—H19119.3
C8—C7—H7120.0C20—C19—H19119.3
C9—C8—C7119.6 (3)C15—C20—C19120.0 (3)
C9—C8—H8120.2C15—C20—H20120.0
C7—C8—H8120.2C19—C20—H20120.0
C8—C9—C10121.0 (3)C18—C21—H21A109.5
C8—C9—H9119.5C18—C21—H21B109.5
C10—C9—H9119.5H21A—C21—H21B109.5
C9—C10—C11120.8 (3)C18—C21—H21C109.5
C9—C10—H10119.6H21A—C21—H21C109.5
C11—C10—H10119.6H21B—C21—H21C109.5
C11—N1—C2—C12−95.9 (3)C8—C9—C10—C111.7 (4)
C11—N1—C2—C13145.9 (2)C2—N1—C11—C10123.8 (3)
C11—N1—C2—C322.4 (3)C2—N1—C11—C6−62.0 (3)
N1—C2—C3—C461.1 (3)C9—C10—C11—N1175.7 (2)
C12—C2—C3—C4−179.4 (2)C9—C10—C11—C61.3 (4)
C13—C2—C3—C4−59.8 (3)C7—C6—C11—N1−178.1 (2)
C2—C3—C4—N5−57.2 (3)N5—C6—C11—N1−0.7 (3)
C2—C3—C4—C14−179.3 (2)C7—C6—C11—C10−3.7 (3)
C3—C4—N5—C6−27.7 (3)N5—C6—C11—C10173.7 (2)
C14—C4—N5—C693.9 (3)O2—S1—C15—C20−1.4 (3)
C3—C4—N5—S1145.32 (18)O1—S1—C15—C20−130.5 (2)
C14—C4—N5—S1−93.1 (3)N5—S1—C15—C20114.2 (2)
O2—S1—N5—C6−146.99 (18)O2—S1—C15—C16177.6 (2)
O1—S1—N5—C6−17.3 (2)O1—S1—C15—C1648.5 (2)
C15—S1—N5—C698.24 (18)N5—S1—C15—C16−66.8 (2)
O2—S1—N5—C440.06 (19)C20—C15—C16—C17−1.0 (4)
O1—S1—N5—C4169.70 (18)S1—C15—C16—C17−180.0 (2)
C15—S1—N5—C4−74.71 (19)C15—C16—C17—C18−0.1 (4)
C4—N5—C6—C7−116.8 (2)C16—C17—C18—C191.0 (4)
S1—N5—C6—C770.3 (3)C16—C17—C18—C21−178.9 (3)
C4—N5—C6—C1165.7 (3)C17—C18—C19—C20−0.8 (5)
S1—N5—C6—C11−107.2 (2)C21—C18—C19—C20179.1 (3)
C11—C6—C7—C83.2 (4)C16—C15—C20—C191.2 (4)
N5—C6—C7—C8−174.3 (2)S1—C15—C20—C19−179.8 (2)
C6—C7—C8—C9−0.1 (4)C18—C19—C20—C15−0.3 (5)
C7—C8—C9—C10−2.3 (5)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C20—H20···O20.932.512.885 (4)105
N1—H1···O2i0.75 (3)2.52 (3)3.268 (3)176 (3)
C14—H14B···O1ii0.962.583.436 (4)149
C13—H13A···Cg20.962.903.7592 (31)150
C19—H19···Cg2i0.932.903.5192 (34)126
Symmetry codes: (i) −x, y+1/2, −z+3/2; (ii) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C20—H20···O20.932.512.885 (4)105
N1—H1···O2i0.75 (3)2.52 (3)3.268 (3)176 (3)
C14—H14B···O1ii0.962.583.436 (4)149
C13—H13A···Cg20.962.903.7592 (31)150
C19—H19···Cg2i0.932.903.5192 (34)126
Symmetry codes: (i) −x, y+1/2, −z+3/2; (ii) x−1, y, z.
Acknowledgements top

KR thanks Dr Babu Varghese, SAIF, IIT-Madras, India, for his help with the data collection and the management of Kandaswami Kandar's College, Velur, Namakkal, India, for their encouragement to pursue the programme.

references
References top

Bassindale, A. (1984). The Third Dimension in Organic Chemistry, ch. 1, p. 11. New York: John Wiley and Sons

Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N. L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573.

Bruker (2004). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.

Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.

Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.

Flack, H. D. (1983). Acta Cryst. A39, 876–881.

Nardelli, M. (1983). Acta Cryst. C39, 1141–1142.

Ponnuswamy, S., Murugadoss, R., Jeyaraman, R., Thiruvalluvar, A. & Parthasarathy, V. (2006). Indian J. Chem. Sect. B, 45, 2059–2070

Rahbaek, L., Breinholt, J., Frisvad, J. C. & Christophersen, C. (1999). J. Org. Chem., 64, 1689–1692

Sheldrick, G. M. (2001). SADABS. University of Göttingen, Germany.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2009). Acta Cryst. D65, 148–155.