N-Isopropyl-6-methyl-2-phenyl­quinoline-3-carboxamide

Benzerka, S.; Bouraiou, A.; Bouacida, S.; Roisnel, T.; Belfaitah, A.

doi:10.1107/S1600536810031582

N-Isopropyl-6-methyl-2-phenylquinoline-3-carboxamide

S. Benzerka, A. Bouraiou, S. Bouacida, T. Roisnel and A. Belfaitah

In the title compound, C₂₀H₂₀N₂O, the dihedral angle between the quinoline ring system and the phenyl ring is 49.40 (5)°. In the crystal structure, zigzag layers of molecules, in which the quinoline units are parallel to the ( $\overline{1}$ 10) plane, are arranged perpendicular to the b axis. Intermolecular N—H

O hydrogen bonds connect the molecules into chains along [010], reinforcing the cohesion between the layers of the structure.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536810031582/lh5101sup1.cif Contains datablock I
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536810031582/lh5101Isup2.hkl Contains datablock I

CCDC reference: 792403

checkCIF report

Key indicators

Single-crystal X-ray study
T = 150 K
Mean (C-C) = 0.002 Å
R factor = 0.050
wR factor = 0.157
Data-to-parameter ratio = 18.5

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       3.58 Ratio
PLAT222_ALERT_3_C Large Non-Solvent    H     Uiso(max)/Uso(min) ...       4.30 Rati
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C18
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          2
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600          4
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          1
              C20 H20 N2 O
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600          4

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   7 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

Comment top

Since Atwell et al. (1988) and Denny et al. (1990) demonstrated the efficacy of 2 + 1 unfused tricyclic aromatic systems such as phenylquinolines as a minimal intercalators, 2-phenylquinoline (Mikata et al., 1998; Henriksen et al., 1991) was selected as the DNA intercalator. The conjugated C=N bond in the 2-phenylquinoline unit was also expected to generate the photoexcited ³(n→π*) state upon photoirradiation, which may have a radical character and could be capable of cleaving DNA (Toshima et al., 1999). On the other hand, certain 2-phenylquinoline carboxamide derivatives have been shown to possess DNA binding capability and a broad-spectrum activity in both leukemia and solid-tumor assays (Atwell et al., 1989). As part of our program related to the synthesis of some new heterocyclic compounds with medicinal potential (Bouraiou et al.,2006, 2008; Benzerka et al., 2008; Ladraa et al., 2009), we report here the synthesis and crystal structure of the title compound (I). The molecular geometry and the atom-numbering scheme of (I) are shown in Fig. 1. The asymmetric unit of title compound contains a quinolyl unit bearing a phenyl ring at position C-2, amide group at C-3 and methyl at C-6. The two rings of the quinolyl moiety are fused in an axial fashion and form a dihedral angle of 3.13 (4)°. The dihedral angle between the phenyl ring quinoline ring system is 49.40 (5)°. The amide group is essentially planar. The r.m.s deviation for atoms C2/C17/O1/N2/C18 is 0.007Å and the maximum deviation is -0.0131 (15)Å for C17. The C—N [1.3260 (17) Å] bond length to the carbonyl group is closer to that of a standard C═N double bond (1.27 Å) than to that of a single bond (1.49 Å). This is because the lone pair electrons on nitrogen of the amide are delocalized into the carbonyl group. The crystal packing can be described as layers in zig zag perpendicular to b axis which quinoline rings are parallel to the (-110) plane (Fig. 2). The crystal packing is stabilized by intermolecular hydrogen bond (N—H···O), resulting in the formation of infinite one-dimensional chain along the b axis linked these layers reinforce the cohesion of the structure (Fig. 2).

Related literature top

For our previous work on the preparation of quinoline derivatives, see: Benzerka et al. (2008); Ladraa et al. (2009); Bouraiou et al. (2006, 2008). For the evaluation of their biological activity, see: Atwell et al. (1988,1989); Denny et al. (1990); Toshima et al. (1999); Mikata et al. (1998); Henriksen et al. (1991). For the synthetic procedure, see: Saudi et al. (2003).

Experimental top

Compound (I) was obtained from 6-methyl-2-phenylquinoline-3-carboxylic acid and ethyl chloroformate in presence triethylamine in chloroform (Saudi et al., 2003). Suitable crystals for X-ray diffraction were obtained by slow evaporation of a solution of (I) in diisopropylether at room temperature.

Structure description top

Computing details top

Data collection: APEX2 (Bruker,2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SIR2002 (Burla et al., 2003); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and DIAMOND (Brandenburg & Berndt, 2001); software used to prepare material for publication: WinGX publication routines (Farrugia, 1999).

Figures top

	Fig. 1. The molecular structure (Farrugia, 1997) of the title compound with the atomic labelling scheme. Displacement are drawn at the 50% probability level.
	Fig. 2. Part of the crystal structure (Brandenburg & Berndt, 2001) showing the layered packing of (I) viewed along the c axis and showing hydrogen bonds [N—H···O] as dashed line along the b axis.

N-Isopropyl-6-methyl-2-phenylquinoline-3-carboxamide top

Crystal data top

C₂₀H₂₀N₂O	F(000) = 1296
M_r = 304.38	D_x = 1.187 Mg m⁻³
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 4726 reflections
a = 12.0007 (3) Å	θ = 3.0–27.3°
b = 9.6314 (2) Å	µ = 0.07 mm⁻¹
c = 29.4627 (8) Å	T = 150 K
V = 3405.40 (14) Å³	Stick, colourless
Z = 8	0.32 × 0.11 × 0.08 mm

Data collection top

Bruker APEXII diffractometer	2839 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.046
CCD rotation images, thin slices scans	θ_max = 27.5°, θ_min = 2.8°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −10→15
T_min = 0.747, T_max = 0.994	k = −7→12
15315 measured reflections	l = −24→38
3906 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.157	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.0914P)² + 0.3352P] where P = (F_o² + 2F_c²)/3
3906 reflections	(Δ/σ)_max = 0.001
211 parameters	Δρ_max = 0.23 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₂₀H₂₀N₂O	V = 3405.40 (14) Å³
M_r = 304.38	Z = 8
Orthorhombic, Pbca	Mo Kα radiation
a = 12.0007 (3) Å	µ = 0.07 mm⁻¹
b = 9.6314 (2) Å	T = 150 K
c = 29.4627 (8) Å	0.32 × 0.11 × 0.08 mm

Data collection top

Bruker APEXII diffractometer	3906 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	2839 reflections with I > 2σ(I)
T_min = 0.747, T_max = 0.994	R_int = 0.046
15315 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.050	0 restraints
wR(F²) = 0.157	H-atom parameters constrained
S = 1.04	Δρ_max = 0.23 e Å⁻³
3906 reflections	Δρ_min = −0.26 e Å⁻³
211 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

	x	y	z	U_iso*/U_eq
O1	0.29293 (9)	−0.22115 (10)	0.10660 (4)	0.0378 (3)
N1	0.58409 (10)	−0.43666 (12)	0.14988 (4)	0.0288 (3)
N2	0.21063 (10)	−0.43091 (12)	0.09977 (4)	0.0309 (3)
H2N	0.2211	−0.5213	0.0984	0.037*
C1	0.47981 (11)	−0.39345 (14)	0.14808 (5)	0.0258 (3)
C2	0.40933 (11)	−0.41975 (13)	0.10973 (5)	0.0240 (3)
C3	0.44903 (12)	−0.50023 (13)	0.07517 (5)	0.0249 (3)
H3	0.4038	−0.5201	0.0504	0.030*
C4	0.55847 (12)	−0.55334 (13)	0.07693 (4)	0.0251 (3)
C5	0.60463 (12)	−0.64177 (14)	0.04333 (5)	0.0289 (3)
H5	0.5619	−0.6654	0.0182	0.035*
C6	0.71088 (13)	−0.69338 (15)	0.04705 (5)	0.0335 (4)
C7	0.77548 (13)	−0.65292 (17)	0.08495 (6)	0.0352 (4)
H7	0.8477	−0.6870	0.0878	0.042*
C8	0.73505 (13)	−0.56529 (16)	0.11750 (5)	0.0332 (4)
H8	0.7805	−0.5384	0.1415	0.040*
C9	0.62453 (11)	−0.51521 (14)	0.11490 (5)	0.0266 (3)
C10	0.75887 (16)	−0.79114 (18)	0.01255 (6)	0.0448 (4)
H10A	0.7119	−0.7928	−0.0138	0.067*
H10B	0.7633	−0.8827	0.0253	0.067*
H10C	0.8321	−0.7604	0.0041	0.067*
C11	0.43566 (13)	−0.32106 (16)	0.18883 (5)	0.0328 (4)
C12	0.33582 (14)	−0.3632 (2)	0.20819 (6)	0.0464 (5)
H12	0.2956	−0.4352	0.1950	0.056*
C13	0.29535 (17)	−0.2991 (3)	0.24697 (7)	0.0681 (7)
H13	0.2292	−0.3291	0.2602	0.082*
C14	0.3541 (2)	−0.1903 (3)	0.26577 (8)	0.0792 (8)
H14	0.3264	−0.1452	0.2913	0.095*
C15	0.4537 (2)	−0.1480 (2)	0.24698 (7)	0.0690 (7)
H15	0.4928	−0.0746	0.2599	0.083*
C16	0.49557 (16)	−0.21433 (18)	0.20900 (6)	0.0454 (4)
H16	0.5639	−0.1874	0.1970	0.055*
C17	0.29824 (12)	−0.34913 (13)	0.10575 (5)	0.0258 (3)
C18	0.09700 (12)	−0.37692 (16)	0.09527 (6)	0.0395 (4)
H18	0.1017	−0.2852	0.0810	0.047*
C19	0.03298 (16)	−0.4717 (2)	0.06337 (11)	0.0859 (9)
H19A	0.0293	−0.5633	0.0762	0.129*
H19B	0.0703	−0.4755	0.0346	0.129*
H19C	−0.0411	−0.4363	0.0592	0.129*
C20	0.04341 (19)	−0.3592 (3)	0.14068 (8)	0.0850 (9)
H20A	0.0880	−0.2983	0.1590	0.128*
H20B	0.0374	−0.4479	0.1553	0.128*
H20C	−0.0296	−0.3201	0.1369	0.128*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0403 (7)	0.0158 (5)	0.0574 (7)	−0.0006 (4)	−0.0080 (5)	0.0015 (4)
N1	0.0269 (6)	0.0314 (6)	0.0281 (6)	−0.0029 (5)	0.0000 (5)	0.0012 (5)
N2	0.0234 (6)	0.0155 (5)	0.0539 (8)	0.0019 (5)	−0.0045 (6)	0.0033 (5)
C1	0.0264 (7)	0.0220 (6)	0.0290 (7)	−0.0029 (5)	−0.0008 (6)	0.0020 (5)
C2	0.0241 (7)	0.0167 (6)	0.0312 (7)	−0.0031 (5)	−0.0019 (6)	0.0030 (5)
C3	0.0287 (7)	0.0185 (6)	0.0276 (7)	−0.0038 (5)	−0.0045 (6)	0.0018 (5)
C4	0.0285 (7)	0.0194 (6)	0.0276 (7)	−0.0035 (6)	0.0024 (6)	0.0046 (5)
C5	0.0338 (8)	0.0236 (7)	0.0293 (7)	−0.0017 (6)	0.0025 (6)	0.0039 (6)
C6	0.0369 (9)	0.0269 (7)	0.0367 (8)	0.0015 (6)	0.0116 (7)	0.0071 (6)
C7	0.0260 (8)	0.0376 (8)	0.0421 (9)	0.0049 (6)	0.0069 (7)	0.0106 (7)
C8	0.0260 (8)	0.0407 (9)	0.0328 (8)	−0.0018 (6)	−0.0001 (6)	0.0064 (6)
C9	0.0260 (7)	0.0254 (7)	0.0283 (7)	−0.0030 (6)	0.0024 (6)	0.0066 (6)
C10	0.0501 (10)	0.0400 (9)	0.0444 (10)	0.0111 (8)	0.0159 (8)	0.0012 (8)
C11	0.0324 (8)	0.0356 (8)	0.0304 (8)	0.0071 (7)	−0.0068 (6)	−0.0031 (6)
C12	0.0364 (10)	0.0642 (12)	0.0387 (10)	0.0050 (8)	0.0019 (7)	−0.0107 (8)
C13	0.0471 (12)	0.112 (2)	0.0449 (11)	0.0199 (12)	0.0061 (9)	−0.0181 (12)
C14	0.0741 (16)	0.115 (2)	0.0487 (13)	0.0337 (15)	−0.0048 (12)	−0.0389 (13)
C15	0.0828 (17)	0.0685 (14)	0.0557 (13)	0.0135 (12)	−0.0237 (12)	−0.0327 (11)
C16	0.0486 (10)	0.0439 (10)	0.0437 (10)	0.0031 (8)	−0.0122 (8)	−0.0103 (8)
C17	0.0289 (8)	0.0179 (6)	0.0307 (7)	0.0003 (5)	−0.0024 (6)	0.0015 (5)
C18	0.0243 (8)	0.0248 (7)	0.0695 (11)	0.0047 (6)	−0.0029 (8)	0.0120 (7)
C19	0.0369 (11)	0.0361 (10)	0.185 (3)	0.0037 (8)	−0.0494 (14)	−0.0047 (14)
C20	0.0510 (13)	0.112 (2)	0.0926 (18)	0.0396 (13)	0.0298 (12)	0.0511 (16)

Geometric parameters (Å, º) top

O1—C17	1.2346 (16)	C10—H10B	0.9600
N1—C1	1.3198 (18)	C10—H10C	0.9600
N1—C9	1.3676 (18)	C11—C12	1.388 (2)
N2—C17	1.3255 (18)	C11—C16	1.388 (2)
N2—C18	1.4654 (18)	C12—C13	1.387 (3)
N2—H2N	0.8800	C12—H12	0.9300
C1—C2	1.4339 (19)	C13—C14	1.379 (4)
C1—C11	1.486 (2)	C13—H13	0.9300
C2—C3	1.3656 (19)	C14—C15	1.378 (4)
C2—C17	1.5012 (19)	C14—H14	0.9300
C3—C4	1.4104 (19)	C15—C16	1.383 (3)
C3—H3	0.9300	C15—H15	0.9300
C4—C5	1.4187 (19)	C16—H16	0.9300
C4—C9	1.419 (2)	C18—C20	1.494 (3)
C5—C6	1.373 (2)	C18—C19	1.519 (3)
C5—H5	0.9300	C18—H18	0.9800
C6—C7	1.414 (2)	C19—H19A	0.9600
C6—C10	1.501 (2)	C19—H19B	0.9600
C7—C8	1.366 (2)	C19—H19C	0.9600
C7—H7	0.9300	C20—H20A	0.9600
C8—C9	1.413 (2)	C20—H20B	0.9600
C8—H8	0.9300	C20—H20C	0.9600
C10—H10A	0.9600

C1—N1—C9	118.72 (12)	C12—C11—C1	120.19 (14)
C17—N2—C18	122.63 (11)	C16—C11—C1	120.57 (15)
C17—N2—H2N	118.7	C13—C12—C11	120.73 (19)
C18—N2—H2N	118.7	C13—C12—H12	119.6
N1—C1—C2	122.37 (13)	C11—C12—H12	119.6
N1—C1—C11	116.96 (12)	C14—C13—C12	119.3 (2)
C2—C1—C11	120.61 (12)	C14—C13—H13	120.3
C3—C2—C1	118.81 (13)	C12—C13—H13	120.3
C3—C2—C17	120.58 (12)	C13—C14—C15	120.4 (2)
C1—C2—C17	120.36 (12)	C13—C14—H14	119.8
C2—C3—C4	120.22 (13)	C15—C14—H14	119.8
C2—C3—H3	119.9	C14—C15—C16	120.2 (2)
C4—C3—H3	119.9	C14—C15—H15	119.9
C3—C4—C5	123.75 (13)	C16—C15—H15	119.9
C3—C4—C9	117.09 (12)	C15—C16—C11	120.01 (19)
C5—C4—C9	119.16 (13)	C15—C16—H16	120.0
C6—C5—C4	121.61 (13)	C11—C16—H16	120.0
C6—C5—H5	119.2	O1—C17—N2	123.72 (13)
C4—C5—H5	119.2	O1—C17—C2	119.78 (12)
C5—C6—C7	118.20 (14)	N2—C17—C2	116.46 (11)
C5—C6—C10	121.96 (15)	N2—C18—C20	111.09 (14)
C7—C6—C10	119.83 (15)	N2—C18—C19	108.26 (13)
C8—C7—C6	121.98 (14)	C20—C18—C19	113.9 (2)
C8—C7—H7	119.0	N2—C18—H18	107.8
C6—C7—H7	119.0	C20—C18—H18	107.8
C7—C8—C9	120.40 (14)	C19—C18—H18	107.8
C7—C8—H8	119.8	C18—C19—H19A	109.5
C9—C8—H8	119.8	C18—C19—H19B	109.5
N1—C9—C8	118.75 (13)	H19A—C19—H19B	109.5
N1—C9—C4	122.61 (13)	C18—C19—H19C	109.5
C8—C9—C4	118.59 (13)	H19A—C19—H19C	109.5
C6—C10—H10A	109.5	H19B—C19—H19C	109.5
C6—C10—H10B	109.5	C18—C20—H20A	109.5
H10A—C10—H10B	109.5	C18—C20—H20B	109.5
C6—C10—H10C	109.5	H20A—C20—H20B	109.5
H10A—C10—H10C	109.5	C18—C20—H20C	109.5
H10B—C10—H10C	109.5	H20A—C20—H20C	109.5
C12—C11—C16	119.20 (16)	H20B—C20—H20C	109.5

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O1ⁱ	0.88	1.95	2.804 (3)	164

Symmetry code: (i) −x+1/2, y−1/2, z.

Experimental details

Crystal data
Chemical formula	C₂₀H₂₀N₂O
M_r	304.38
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	150
a, b, c (Å)	12.0007 (3), 9.6314 (2), 29.4627 (8)
V (Å³)	3405.40 (14)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.07
Crystal size (mm)	0.32 × 0.11 × 0.08

Data collection
Diffractometer	Bruker APEXII
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.747, 0.994
No. of measured, independent and observed [I > 2σ(I)] reflections	15315, 3906, 2839
R_int	0.046
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.050, 0.157, 1.04
No. of reflections	3906
No. of parameters	211
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.26

Computer programs: APEX2 (Bruker,2001), SAINT (Bruker, 2001), SIR2002 (Burla et al., 2003), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997) and DIAMOND (Brandenburg & Berndt, 2001), WinGX publication routines (Farrugia, 1999).