Crystal structure of 2-(4-methyl­piperazin-1-yl)quinoline-3-carbaldehyde

In the title compound, C₁₅H₁₇N₃O, the aldehyde group is twisted relative to the quinoline group by17.6 (2)° due to the presence of a bulky piperazinyl group in the ortho position. The piperazine N atom attached to the aromatic ring is sp³-hybridized and the dihedral angle between the mean planes through the the six piperazine ring atoms and through the quinoline ring system is 40.59 (7)°. Both piperazine substituents are in equatorial positions.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.054
• wR factor = 0.162
• Data-to-parameter ratio = 12.6

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Alert level C
THETM01_ALERT_3_C  The value of sine(theta_max)/wavelength is less than 0.590
            Calculated sin(theta_max)/wavelength =    0.5853
PLAT029_ALERT_3_C _diffrn_measured_fraction_theta_full Low .......      0.975 Note
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.585         53 Report
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          1 Note

Alert level G
PLAT066_ALERT_1_G Predicted and Reported Tmin&Tmax Range Identical          ? Check
PLAT072_ALERT_2_G SHELXL First  Parameter in WGHT Unusually Large.       0.12 Report
PLAT899_ALERT_4_G SHELXL97   is Deprecated and Succeeded by SHELXL       2014 Note
PLAT909_ALERT_3_G Percentage of Observed Data at Theta(Max) still          47 %

   0 ALERT level A = Most likely a serious problem - resolve or explain
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   4 ALERT level G = General information/check it is not something unexpected

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
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PUBL024_ALERT_1_A The number of authors is greater than 5.
              Please specify the role of each of the co-authors
              for your paper.

Author Response: RND and SS synthesized and characterized the compound. SN and NKL collected the data. PAS and DBAK solved and analyzed the data.

   1 ALERT level A = Data missing that is essential or data in wrong format
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S1. Introduction

Quinoline and its derivatives have been well known in pharmaceutical chemistry because of their wide spectrum of biological activities and their presence in naturally occurring compounds. They have been shown to possess anti­malarial (Nasveld et al., 2005), anti­biotic (Eswaran et al., 2009), anti­cancer (Denny et al., 1983), anti-inflammatory (Muruganantham et al., 2004), anti­hypertensive (Maguire et al., 1994), tyrokinase PDGF-RTK inhibition (Wilson et al., 1992) and anti-HIV properties (Strekowski et al., 1991). In addition, polysubstituted quinoline can achieve hierchical self-assembly into variety of meso and nano structures with enhanced photonic and electronic properties (Gyoten et al., 2003). In this view the title compound was synthesized to study its crystal structure.

S2. Experimental

S2.1. Synthesis and crystallization

2-Chloro­quinoline-3-carbaldehyde (0.42 g, 0.00351 mmol), N-methyl piperazine (0.14 g, 0.00351 mmol) and anhydrous K₂CO₃ (1.0 g, 0.002920 mmol) were refluxed for 24 hrs in DMF. The progress of the reaction was monitored by thin layer chromatography. After the completion of the reaction, the reaction mixture was poured into water and extracted to ethyl acetate. The organic layer was washed with water, dried and concentrated under vacuum using rotary evaporator. Single crystals of the title compound were obtained by slow evaporation of the ethyl acetate solution at room temperature (27^oC).

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms were positioned with idealized geometry using a riding model with C—H = 0.93-0.97 Å. All H atoms were refined with isotropic displacement parameters (set to 1.2 times of the Ueq of the parent C atom).

S3. Results and discussion

The crystal packing of the compound does not feature any specific strong or weak inter­molecular inter­actions.

Related literature

For biological activity of quinoline derivatives, see: Nasveld et al. (2005); Eswaran et al. (2009); Leatham et al. (1983); Muruganantham et al. (2004); Maguire et al. (1994); Wilson et al. (1992); Strekowski et al. (1991). For photonic and electronic properties of poly-substituted quinolines, see: Gyoten et al. (2003).

Structure description

Quinoline and its derivatives have been well known in pharmaceutical chemistry because of their wide spectrum of biological activities and their presence in naturally occurring compounds. They have been shown to possess anti­malarial (Nasveld et al., 2005), anti­biotic (Eswaran et al., 2009), anti­cancer (Denny et al., 1983), anti-inflammatory (Muruganantham et al., 2004), anti­hypertensive (Maguire et al., 1994), tyrokinase PDGF-RTK inhibition (Wilson et al., 1992) and anti-HIV properties (Strekowski et al., 1991). In addition, polysubstituted quinoline can achieve hierchical self-assembly into variety of meso and nano structures with enhanced photonic and electronic properties (Gyoten et al., 2003). In this view the title compound was synthesized to study its crystal structure.

The crystal packing of the compound does not feature any specific strong or weak inter­molecular inter­actions.

For biological activity of quinoline derivatives, see: Nasveld et al. (2005); Eswaran et al. (2009); Leatham et al. (1983); Muruganantham et al. (2004); Maguire et al. (1994); Wilson et al. (1992); Strekowski et al. (1991). For photonic and electronic properties of poly-substituted quinolines, see: Gyoten et al. (2003).

Synthesis and crystallization

2-Chloro­quinoline-3-carbaldehyde (0.42 g, 0.00351 mmol), N-methyl piperazine (0.14 g, 0.00351 mmol) and anhydrous K₂CO₃ (1.0 g, 0.002920 mmol) were refluxed for 24 hrs in DMF. The progress of the reaction was monitored by thin layer chromatography. After the completion of the reaction, the reaction mixture was poured into water and extracted to ethyl acetate. The organic layer was washed with water, dried and concentrated under vacuum using rotary evaporator. Single crystals of the title compound were obtained by slow evaporation of the ethyl acetate solution at room temperature (27^oC).

Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms were positioned with idealized geometry using a riding model with C—H = 0.93-0.97 Å. All H atoms were refined with isotropic displacement parameters (set to 1.2 times of the Ueq of the parent C atom).

Computing details

Data collection: APEX2 (Bruker, 2009); cell refinement: APEX2 and SAINT-Plus (Bruker, 2009); data reduction: SAINT-Plus and XPREP (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

Fig. 1. Molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level.

2-(4-Methylpiperazin-1-yl)quinoline-3-carbaldehyde

Crystal data

C15H17N3O	Prism
Mr = 255.32	Dx = 1.269 Mg m^−3
Monoclinic, P21/n	Melting point: 384 K
Hall symbol: -P 2yn	Cu Kα radiation, λ = 1.54178 Å
a = 12.3282 (4) Å	Cell parameters from 143 reflections
b = 5.8935 (2) Å	θ = 3.9–64.5°
c = 18.9202 (7) Å	µ = 0.65 mm^−1
β = 103.591 (2)°	T = 296 K
V = 1336.18 (8) Å^3	Prism, colourless
Z = 4	0.28 × 0.26 × 0.24 mm
F(000) = 544

Data collection

Bruker APEXII CCD diffractometer	2181 independent reflections
Radiation source: fine-focus sealed tube	1859 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.048
phi and φ scans	θmax = 64.5°, θmin = 3.9°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −14→14
Tmin = 0.838, Tmax = 0.859	k = −6→6
9762 measured reflections	l = −21→21

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)] = 0.054	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.162	H-atom parameters constrained
S = 1.06	w = 1/[σ^2(Fo^2) + (0.1151P)^2 + 0.0654P] where P = (Fo^2 + 2Fc^2)/3
2181 reflections	(Δ/σ)max < 0.001
173 parameters	Δρmax = 0.22 e Å^−3
0 restraints	Δρmin = −0.24 e Å^−3

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.44347 (10)	0.7887 (2)	0.60405 (6)	0.0446 (4)
N2	0.31637 (10)	0.4894 (2)	0.58318 (6)	0.0443 (4)
N3	0.15374 (11)	0.2821 (2)	0.46867 (7)	0.0492 (4)
O1	0.33529 (13)	0.4038 (3)	0.79890 (7)	0.0800 (5)
C1	0.38623 (12)	0.6362 (3)	0.63074 (7)	0.0415 (4)
C2	0.39605 (12)	0.6082 (3)	0.70773 (8)	0.0435 (4)
C3	0.46317 (13)	0.7537 (3)	0.75426 (8)	0.0456 (4)
H3	0.4690	0.7410	0.8040	0.055*
C4	0.52382 (12)	0.9229 (3)	0.72789 (8)	0.0429 (4)
C5	0.59503 (14)	1.0786 (3)	0.77313 (9)	0.0517 (5)
H5	0.6035	1.0718	0.8232	0.062*
C6	0.65119 (15)	1.2380 (3)	0.74416 (10)	0.0571 (5)
H6	0.6980	1.3397	0.7744	0.068*
C7	0.63874 (16)	1.2497 (3)	0.66853 (10)	0.0580 (5)
H7	0.6768	1.3606	0.6490	0.070*
C8	0.57153 (14)	1.1003 (3)	0.62334 (9)	0.0516 (5)
H8	0.5648	1.1094	0.5734	0.062*
C9	0.51232 (12)	0.9326 (3)	0.65156 (8)	0.0430 (4)
C10	0.19665 (13)	0.5037 (3)	0.58101 (8)	0.0477 (4)
H10A	0.1659	0.6413	0.5560	0.057*
H10B	0.1861	0.5100	0.6302	0.057*
C11	0.13648 (13)	0.3007 (3)	0.54226 (9)	0.0517 (5)
H11A	0.1635	0.1642	0.5694	0.062*
H11B	0.0573	0.3142	0.5399	0.062*
C12	0.27299 (14)	0.2697 (3)	0.47221 (9)	0.0522 (5)
H12A	0.2846	0.2582	0.4234	0.063*
H12B	0.3038	0.1347	0.4988	0.063*
C13	0.33266 (14)	0.4768 (3)	0.50926 (8)	0.0516 (5)
H13A	0.4117	0.4670	0.5106	0.062*
H13B	0.3031	0.6123	0.4824	0.062*
C14	0.09682 (18)	0.0831 (4)	0.43236 (9)	0.0660 (6)
H14A	0.1106	0.0708	0.3846	0.099*
H14B	0.0181	0.0973	0.4285	0.099*
H14C	0.1242	−0.0501	0.4600	0.099*
C15	0.34545 (14)	0.4132 (3)	0.73732 (9)	0.0561 (5)
H15	0.3201	0.2913	0.7067	0.067*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0470 (7)	0.0482 (8)	0.0386 (7)	−0.0039 (6)	0.0102 (6)	0.0002 (5)
N2	0.0423 (7)	0.0538 (9)	0.0381 (7)	−0.0054 (6)	0.0119 (5)	−0.0038 (6)
N3	0.0541 (8)	0.0505 (9)	0.0400 (7)	−0.0114 (6)	0.0047 (6)	0.0021 (6)
O1	0.0885 (10)	0.1024 (13)	0.0487 (8)	−0.0299 (8)	0.0151 (7)	0.0178 (7)
C1	0.0400 (8)	0.0462 (9)	0.0389 (8)	0.0020 (6)	0.0102 (6)	0.0015 (6)
C2	0.0408 (8)	0.0503 (10)	0.0392 (8)	0.0025 (6)	0.0088 (6)	0.0038 (7)
C3	0.0456 (9)	0.0556 (10)	0.0348 (8)	0.0055 (7)	0.0076 (6)	0.0042 (7)
C4	0.0402 (8)	0.0467 (9)	0.0407 (8)	0.0049 (6)	0.0077 (6)	0.0001 (6)
C5	0.0529 (10)	0.0568 (11)	0.0431 (8)	0.0002 (8)	0.0064 (7)	−0.0061 (7)
C6	0.0583 (10)	0.0557 (11)	0.0549 (10)	−0.0102 (8)	0.0086 (8)	−0.0100 (8)
C7	0.0640 (11)	0.0530 (11)	0.0576 (10)	−0.0139 (8)	0.0155 (8)	−0.0007 (8)
C8	0.0574 (10)	0.0544 (11)	0.0439 (8)	−0.0055 (8)	0.0142 (7)	0.0014 (7)
C9	0.0427 (8)	0.0458 (10)	0.0402 (8)	0.0020 (6)	0.0090 (6)	−0.0002 (6)
C10	0.0450 (9)	0.0568 (11)	0.0420 (8)	−0.0011 (7)	0.0117 (6)	0.0002 (7)
C11	0.0481 (9)	0.0603 (11)	0.0465 (9)	−0.0097 (7)	0.0108 (7)	0.0025 (7)
C12	0.0614 (10)	0.0561 (11)	0.0402 (8)	−0.0041 (7)	0.0143 (7)	−0.0042 (7)
C13	0.0513 (9)	0.0644 (11)	0.0424 (8)	−0.0112 (8)	0.0180 (7)	−0.0056 (7)
C14	0.0820 (13)	0.0605 (12)	0.0491 (10)	−0.0239 (9)	0.0026 (9)	0.0008 (8)
C15	0.0567 (10)	0.0634 (12)	0.0449 (9)	−0.0096 (8)	0.0050 (7)	0.0107 (8)

Geometric parameters (Å, º)

N1—C1	1.315 (2)	C6—H6	0.9300
N1—C9	1.375 (2)	C7—C8	1.364 (3)
N2—C1	1.391 (2)	C7—H7	0.9300
N2—C13	1.4607 (18)	C8—C9	1.406 (2)
N2—C10	1.4693 (19)	C8—H8	0.9300
N3—C14	1.454 (2)	C10—C11	1.505 (2)
N3—C12	1.458 (2)	C10—H10A	0.9700
N3—C11	1.461 (2)	C10—H10B	0.9700
O1—C15	1.202 (2)	C11—H11A	0.9700
C1—C2	1.442 (2)	C11—H11B	0.9700
C2—C3	1.361 (2)	C12—C13	1.510 (2)
C2—C15	1.479 (2)	C12—H12A	0.9700
C3—C4	1.406 (2)	C12—H12B	0.9700
C3—H3	0.9300	C13—H13A	0.9700
C4—C5	1.411 (2)	C13—H13B	0.9700
C4—C9	1.419 (2)	C14—H14A	0.9600
C5—C6	1.357 (3)	C14—H14B	0.9600
C5—H5	0.9300	C14—H14C	0.9600
C6—C7	1.404 (3)	C15—H15	0.9300
C1—N1—C9	118.40 (12)	N2—C10—C11	110.18 (13)
C1—N2—C13	116.58 (12)	N2—C10—H10A	109.6
C1—N2—C10	116.60 (12)	C11—C10—H10A	109.6
C13—N2—C10	109.84 (11)	N2—C10—H10B	109.6
C14—N3—C12	110.53 (15)	C11—C10—H10B	109.6
C14—N3—C11	110.40 (13)	H10A—C10—H10B	108.1
C12—N3—C11	109.34 (12)	N3—C11—C10	111.00 (13)
N1—C1—N2	118.89 (12)	N3—C11—H11A	109.4
N1—C1—C2	122.74 (14)	C10—C11—H11A	109.4
N2—C1—C2	118.32 (13)	N3—C11—H11B	109.4
C3—C2—C1	118.36 (14)	C10—C11—H11B	109.4
C3—C2—C15	119.41 (14)	H11A—C11—H11B	108.0
C1—C2—C15	121.90 (15)	N3—C12—C13	110.89 (14)
C2—C3—C4	120.69 (14)	N3—C12—H12A	109.5
C2—C3—H3	119.7	C13—C12—H12A	109.5
C4—C3—H3	119.7	N3—C12—H12B	109.5
C3—C4—C5	123.55 (14)	C13—C12—H12B	109.5
C3—C4—C9	117.08 (14)	H12A—C12—H12B	108.0
C5—C4—C9	119.36 (15)	N2—C13—C12	108.90 (13)
C6—C5—C4	120.59 (15)	N2—C13—H13A	109.9
C6—C5—H5	119.7	C12—C13—H13A	109.9
C4—C5—H5	119.7	N2—C13—H13B	109.9
C5—C6—C7	120.09 (16)	C12—C13—H13B	109.9
C5—C6—H6	120.0	H13A—C13—H13B	108.3
C7—C6—H6	120.0	N3—C14—H14A	109.5
C8—C7—C6	120.80 (16)	N3—C14—H14B	109.5
C8—C7—H7	119.6	H14A—C14—H14B	109.5
C6—C7—H7	119.6	N3—C14—H14C	109.5
C7—C8—C9	120.59 (15)	H14A—C14—H14C	109.5
C7—C8—H8	119.7	H14B—C14—H14C	109.5
C9—C8—H8	119.7	O1—C15—C2	123.51 (18)
N1—C9—C8	118.78 (13)	O1—C15—H15	118.2
N1—C9—C4	122.64 (14)	C2—C15—H15	118.2
C8—C9—C4	118.56 (15)