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Acta Cryst. (2008). E64, o580    [ doi:10.1107/S1600536808003954 ]

1-(4-Bromobenzoyl)-2-phenylpyrrolidine-2-carboxamide

R. Tamazyan, A. Ayvazyan, A. Martirosyan, G. Harutunyan and V. Martirosyan

Abstract top

In the title compound, C18H17BrN2O2, which is a potential human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor, the pyrrolidine ring exhibits an envelope conformation. In the crystal structure, intermolecular N-H...O hydrogen bonds [N...O = 2.861 (3) Å] link the molecules into centrosymmetric dimers.

Comment top

The title compound, (I), belongs to a family of non-nucleoside reverse transcriptase inhibitors (NNRTIs), which exhibit potential HIV-1 RT inhibition properties (De Clercq, 1996).

In (I) (Fig. 1), all bond lengths and angles are in good agreement with those observed in the related compounds (Karapetyan et al., 2002; Tamazyan et al., 2002, 2007). Both H atoms of amide group, H7b and H7a, respectively, are involved in intra- and intermolecular N—H···O hydrogen bonds (Table 1). The latter one links the molecules into centrosymmetric dimers (Fig. 2).

Related literature top

For related crystal structures, see: Karapetyan et al. (2002); Tamazyan et al. (2002, 2007). For details of the synthesis, see Martirosyan et al. (2000, 2004). For potential pharmacological applications, see De Clercq (1996).

Experimental top

The title compound was synthesized by cycloalkylation of N1-(3-chloropropyl)-N1-cyano(phenyl)methyl-4-bromobenzamide in phase transfer catalyses condition to 1-(4-bromobenzoyl)-2-phenyl-2-pyrrolidinecarbonitrile and then by hydrolizes with concentric sulfuric acid (Martirosyan et al., 2000, 2004). The compound as synthesized is a racemic mixture of optical isomers (R and S) of 1-(4-bromobenzoyl)-2-phenyl-2-pyrrolidinecarboxamide molecule. The crystals were grown from methanol solution. The suitable sample with spherical shape of the size ~0.28 mm was prepared and selected for X-ray diffraction experiment.

Refinement top

All H atoms were located on a difference map. Atoms H7a and H7b were refined isotropically. C-bound H atoms were placed in idealized positions (C—H 0.93–0.97 Å) and refined as riding, with Uiso = 1.2 Ueq(C).

Computing details top

Data collection: DATACOL in CAD-4 (Enraf–Nonius, 1988); cell refinement: LS in CAD-4 (Enraf–Nonius, 1988); data reduction: HELENA (Spek, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) showing the atomic numbering and displacement ellipsoids at the 50% probability level. H atoms omitted for clarity.
[Figure 2] Fig. 2. Hydrogen-bonded (dashed lines) dimer in the crystal structure of (I) [symmetry code: (i) -x, 1 - y, 1 - z]. Only H atoms participating in hydrogen-bonding are shown.
1-(4-Bromobenzoyl)-2-phenylpyrrolidine-2-carboxamide top
Crystal data top
C18H17BrN2O2F000 = 760
Mr = 373.25Dx = 1.428 Mg m−3
Monoclinic, P21/cMo Kα radiation
λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 25 reflections
a = 9.5707 (19) Åθ = 13–16º
b = 13.738 (3) ŵ = 2.38 mm−1
c = 13.302 (3) ÅT = 260 (2) K
β = 96.99 (2)ºSpherical, colourless
V = 1736.0 (6) Å30.28 × 0.28 × 0.28 × 0.14 (radius) mm
Z = 4
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.050
Radiation source: fine-focus sealed tubeθmax = 28.0º
Monochromator: graphiteθmin = 2.1º
T = 260(2) Kh = −12→12
θ/2θ scansk = 0→18
Absorption correction: for a sphere
(SHELXTL; Sheldrick, 2008)		l = −17→17
Tmin = 0.612, Tmax = 0.6173 standard reflections
8356 measured reflections every 180 min
4180 independent reflections intensity decay: none
2941 reflections with I > 2σ(I)
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.046H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.119  w = 1/[σ2(Fo2) + (0.0458P)2 + 1.2016P]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max = 0.001
4180 reflectionsΔρmax = 0.87 e Å−3
216 parametersΔρmin = −0.89 e Å−3
10 restraintsExtinction correction: none
Primary atom site location: structure-invariant direct methods
Crystal data top
C18H17BrN2O2V = 1736.0 (6) Å3
Mr = 373.25Z = 4
Monoclinic, P21/cMo Kα
a = 9.5707 (19) ŵ = 2.38 mm−1
b = 13.738 (3) ÅT = 260 (2) K
c = 13.302 (3) Å0.28 × 0.28 × 0.28 × 0.14 (radius) mm
β = 96.99 (2)º
Data collection top
Enraf–Nonius CAD-4
diffractometer		2941 reflections with I > 2σ(I)
Absorption correction: for a sphere
(SHELXTL; Sheldrick, 2008)		Rint = 0.050
Tmin = 0.612, Tmax = 0.6173 standard reflections
8356 measured reflections every 180 min
4180 independent reflections intensity decay: none
Refinement top
R[F2 > 2σ(F2)] = 0.04610 restraints
wR(F2) = 0.119H atoms treated by a mixture of
independent and constrained refinement
S = 1.02Δρmax = 0.87 e Å−3
4180 reflectionsΔρmin = −0.89 e Å−3
216 parameters
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
Br10.68968 (4)1.01480 (3)0.85408 (3)0.07187 (17)
C1−0.0555 (2)0.71666 (16)0.64026 (16)0.0217 (4)
N20.08435 (19)0.75423 (14)0.68588 (13)0.0230 (4)
C30.1138 (3)0.7265 (2)0.79443 (18)0.0372 (6)
H3A0.11120.78310.83790.045*
H3B0.20510.69550.80840.045*
C4−0.0033 (3)0.65609 (19)0.80987 (18)0.0330 (5)
H4A−0.02570.65810.87900.040*
H4B0.02150.59000.79350.040*
C5−0.1249 (3)0.69388 (18)0.73599 (17)0.0277 (5)
H5A−0.16560.75200.76200.033*
H5B−0.19770.64490.72240.033*
C6−0.0375 (2)0.62094 (16)0.58089 (16)0.0225 (5)
N70.0475 (3)0.62518 (17)0.50977 (16)0.0310 (5)
H7A0.060 (3)0.572 (2)0.477 (2)0.026 (7)*
H7B0.089 (3)0.677 (2)0.502 (2)0.038 (8)*
O8−0.1011 (2)0.54709 (12)0.60012 (14)0.0357 (4)
C9−0.1430 (2)0.78995 (16)0.57304 (17)0.0245 (5)
C10−0.1242 (3)0.88979 (18)0.5831 (2)0.0333 (5)
H10−0.05150.91390.62910.040*
C11−0.2120 (3)0.9539 (2)0.5257 (2)0.0448 (7)
H11−0.19751.02060.53280.054*
C12−0.3217 (3)0.9190 (2)0.4578 (2)0.0484 (8)
H12−0.38110.96210.41930.058*
C13−0.3422 (3)0.8208 (2)0.4475 (2)0.0454 (7)
H13−0.41600.79730.40210.055*
C14−0.2534 (3)0.75578 (19)0.50447 (19)0.0341 (6)
H14−0.26800.68910.49660.041*
C150.1780 (2)0.79997 (16)0.63414 (17)0.0244 (5)
O160.16487 (18)0.80521 (12)0.54045 (12)0.0298 (4)
C170.3019 (2)0.84793 (17)0.69371 (18)0.0264 (5)
C180.4350 (3)0.8311 (2)0.6659 (2)0.0356 (6)
H180.44630.78670.61480.043*
C190.5505 (3)0.8797 (2)0.7137 (2)0.0441 (7)
H190.63970.86790.69550.053*
C200.5317 (3)0.9461 (2)0.7890 (2)0.0412 (7)
C210.4003 (3)0.9652 (2)0.8166 (2)0.0410 (6)
H210.38921.01100.86660.049*
C220.2853 (3)0.91537 (19)0.7691 (2)0.0337 (6)
H220.19620.92710.78770.040*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.0470 (2)0.0818 (3)0.0793 (3)−0.02922 (18)−0.02262 (18)0.0072 (2)
C10.0249 (10)0.0220 (11)0.0184 (10)−0.0011 (8)0.0038 (8)−0.0017 (8)
N20.0263 (9)0.0274 (10)0.0154 (9)−0.0030 (8)0.0033 (7)−0.0008 (7)
C30.0455 (15)0.0498 (16)0.0152 (11)−0.0080 (12)−0.0002 (10)0.0018 (11)
C40.0441 (14)0.0370 (14)0.0188 (11)−0.0031 (11)0.0070 (10)0.0039 (10)
C50.0329 (12)0.0292 (12)0.0229 (11)0.0000 (10)0.0108 (9)−0.0012 (9)
C60.0273 (11)0.0230 (11)0.0170 (10)0.0020 (9)0.0014 (8)0.0005 (8)
N70.0464 (13)0.0213 (11)0.0280 (11)−0.0039 (10)0.0159 (9)−0.0048 (9)
O80.0492 (11)0.0245 (9)0.0365 (10)−0.0080 (8)0.0176 (8)−0.0047 (7)
C90.0266 (11)0.0263 (11)0.0216 (11)0.0033 (9)0.0070 (9)0.0019 (9)
C100.0359 (13)0.0281 (13)0.0367 (14)0.0033 (10)0.0076 (11)0.0004 (11)
C110.0519 (17)0.0289 (13)0.0556 (19)0.0102 (12)0.0146 (15)0.0123 (13)
C120.0484 (17)0.0498 (18)0.0472 (17)0.0196 (14)0.0065 (14)0.0200 (14)
C130.0398 (15)0.0563 (19)0.0375 (16)0.0111 (13)−0.0064 (12)0.0058 (13)
C140.0359 (13)0.0332 (13)0.0324 (13)0.0040 (11)0.0011 (11)−0.0017 (11)
C150.0282 (11)0.0221 (11)0.0237 (11)0.0022 (9)0.0063 (9)−0.0015 (9)
O160.0383 (9)0.0314 (9)0.0208 (8)−0.0058 (7)0.0078 (7)−0.0010 (7)
C170.0257 (11)0.0270 (11)0.0267 (11)0.0000 (9)0.0042 (9)0.0001 (10)
C180.0310 (13)0.0372 (14)0.0398 (15)0.0024 (11)0.0095 (11)−0.0016 (11)
C190.0244 (12)0.0528 (17)0.0552 (18)0.0022 (11)0.0060 (12)0.0068 (15)
C200.0299 (13)0.0445 (15)0.0453 (16)−0.0118 (11)−0.0107 (11)0.0070 (13)
C210.0430 (15)0.0394 (15)0.0392 (15)−0.0072 (12)−0.0001 (12)−0.0086 (12)
C220.0287 (12)0.0357 (13)0.0374 (14)−0.0013 (10)0.0064 (10)−0.0093 (11)
Geometric parameters (Å, °) top
Br1—C201.899 (3)C10—C111.382 (4)
C1—N21.493 (3)C10—H100.9300
C1—C91.527 (3)C11—C121.385 (5)
C1—C51.538 (3)C11—H110.9300
C1—C61.554 (3)C12—C131.368 (5)
N2—C151.350 (3)C12—H120.9300
N2—C31.487 (3)C13—C141.392 (4)
C3—C41.513 (4)C13—H130.9300
C3—H3A0.9700C14—H140.9300
C3—H3B0.9700C15—O161.239 (3)
C4—C51.520 (3)C15—C171.496 (3)
C4—H4A0.9700C17—C181.388 (3)
C4—H4B0.9700C17—C221.389 (3)
C5—H5A0.9700C18—C191.378 (4)
C5—H5B0.9700C18—H180.9300
C6—O81.226 (3)C19—C201.383 (4)
C6—N71.321 (3)C19—H190.9300
N7—H7A0.86 (3)C20—C211.378 (4)
N7—H7B0.83 (3)C21—C221.383 (4)
C9—C101.388 (3)C21—H210.9300
C9—C141.391 (3)C22—H220.9300
N2—C1—C9114.23 (18)C11—C10—C9121.0 (3)
N2—C1—C5100.93 (17)C11—C10—H10119.5
C9—C1—C5110.99 (18)C9—C10—H10119.5
N2—C1—C6110.43 (17)C10—C11—C12120.1 (3)
C9—C1—C6110.32 (17)C10—C11—H11120.0
C5—C1—C6109.54 (18)C12—C11—H11120.0
C15—N2—C3123.7 (2)C13—C12—C11119.6 (3)
C15—N2—C1124.89 (18)C13—C12—H12120.2
C3—N2—C1111.14 (18)C11—C12—H12120.2
N2—C3—C4103.87 (19)C12—C13—C14120.6 (3)
N2—C3—H3A111.0C12—C13—H13119.7
C4—C3—H3A111.0C14—C13—H13119.7
N2—C3—H3B111.0C9—C14—C13120.3 (3)
C4—C3—H3B111.0C9—C14—H14119.8
H3A—C3—H3B109.0C13—C14—H14119.8
C3—C4—C5102.4 (2)O16—C15—N2123.2 (2)
C3—C4—H4A111.3O16—C15—C17118.9 (2)
C5—C4—H4A111.3N2—C15—C17117.9 (2)
C3—C4—H4B111.3C18—C17—C22119.5 (2)
C5—C4—H4B111.3C18—C17—C15118.6 (2)
H4A—C4—H4B109.2C22—C17—C15121.5 (2)
C4—C5—C1103.39 (19)C19—C18—C17120.5 (3)
C4—C5—H5A111.1C19—C18—H18119.8
C1—C5—H5A111.1C17—C18—H18119.8
C4—C5—H5B111.1C18—C19—C20119.1 (3)
C1—C5—H5B111.1C18—C19—H19120.5
H5A—C5—H5B109.1C20—C19—H19120.5
O8—C6—N7123.4 (2)C21—C20—C19121.5 (2)
O8—C6—C1120.3 (2)C21—C20—Br1119.0 (2)
N7—C6—C1116.3 (2)C19—C20—Br1119.5 (2)
C6—N7—H7A117.1 (18)C20—C21—C22119.0 (3)
C6—N7—H7B119 (2)C20—C21—H21120.5
H7A—N7—H7B124 (3)C22—C21—H21120.5
C10—C9—C14118.4 (2)C21—C22—C17120.4 (2)
C10—C9—C1122.7 (2)C21—C22—H22119.8
C14—C9—C1118.7 (2)C17—C22—H22119.8
C9—C1—N2—C15−49.1 (3)C1—C9—C10—C11−175.3 (2)
C5—C1—N2—C15−168.3 (2)C9—C10—C11—C120.7 (4)
C6—C1—N2—C1575.9 (3)C10—C11—C12—C13−0.2 (5)
C9—C1—N2—C3136.3 (2)C11—C12—C13—C14−0.3 (5)
C5—C1—N2—C317.2 (2)C10—C9—C14—C130.1 (4)
C6—C1—N2—C3−98.6 (2)C1—C9—C14—C13175.0 (2)
C15—N2—C3—C4−165.7 (2)C12—C13—C14—C90.3 (4)
C1—N2—C3—C49.0 (3)C3—N2—C15—O16164.8 (2)
N2—C3—C4—C5−31.7 (3)C1—N2—C15—O16−9.1 (3)
C3—C4—C5—C143.1 (2)C3—N2—C15—C17−16.3 (3)
N2—C1—C5—C4−36.6 (2)C1—N2—C15—C17169.74 (19)
C9—C1—C5—C4−158.09 (19)O16—C15—C17—C18−48.8 (3)
C6—C1—C5—C479.8 (2)N2—C15—C17—C18132.3 (2)
N2—C1—C6—O8125.4 (2)O16—C15—C17—C22125.0 (3)
C9—C1—C6—O8−107.4 (2)N2—C15—C17—C22−53.9 (3)
C5—C1—C6—O815.1 (3)C22—C17—C18—C191.0 (4)
N2—C1—C6—N7−55.3 (3)C15—C17—C18—C19174.9 (2)
C9—C1—C6—N771.9 (3)C17—C18—C19—C20−0.6 (4)
C5—C1—C6—N7−165.6 (2)C18—C19—C20—C21−0.5 (4)
N2—C1—C9—C10−23.9 (3)C18—C19—C20—Br1−179.2 (2)
C5—C1—C9—C1089.4 (3)C19—C20—C21—C221.2 (4)
C6—C1—C9—C10−149.0 (2)Br1—C20—C21—C22179.9 (2)
N2—C1—C9—C14161.4 (2)C20—C21—C22—C17−0.8 (4)
C5—C1—C9—C14−85.3 (3)C18—C17—C22—C21−0.3 (4)
C6—C1—C9—C1436.3 (3)C15—C17—C22—C21−174.0 (2)
C14—C9—C10—C11−0.6 (4)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N7—H7b···O160.83 (2)1.95 (3)2.726 (3)155 (3)
N7—H7a···O8i0.86 (3)2.00 (3)2.861 (3)176 (3)
Symmetry codes: (i) −x, −y+1, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N7—H7b···O160.83 (2)1.95 (3)2.726 (3)155 (3)
N7—H7a···O8i0.86 (3)2.00 (3)2.861 (3)176 (3)
Symmetry codes: (i) −x, −y+1, −z+1.
Acknowledgements top

This work was supported by the Armenian Science and Education Foundation (ANSEF) (grant No. PS-chemorg-907).

references
References top

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