2-[2-(4-Methyl­piperazin-1-yl)eth­yl]iso­indoline-1,3-dione

Zhou, M.; Shao, Y.; Xia, Y.; Liu, X.-L.; Sun, X.-Q.

doi:10.1107/S1600536814002232

organic compounds

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ISSN: 2056-9890

Volume 70| Part 3| March 2014| Page o287

doi:10.1107/S1600536814002232

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2-[2-(4-Methylpiperazin-1-yl)ethyl]isoindoline-1,3-dione

Mi Zhou,^a Ying Shao,^a ^* Yong-an Xia,^a Xiao-Long Liu ^a and Xiao-Qiang Sun ^a

^aKey Laboratory of Fine Petrochemical Engineering, Changzhou University, Changzhou 213164, Jiangsu, People's Republic of China
^*Correspondence e-mail: shaoying810724@163.com

(Received 15 April 2013; accepted 30 January 2014; online 12 February 2014)

In the title compound, C₁₅H₁₉N₃O₂, the piperazine ring adopts a chair conformation, with its N—C bonds in pseudo-equatorial orientations. The dihedral angle between the C atoms of the piperazine ring and the phthalamide ring system (r.m.s. deviaiton = 0.008 Å) is 89.30 (8)°. In the crystal, molecules are linked by C—H⋯O hydrogen bonds, generating a three-dimensional network and aromatic π–π interactions also occur [centroid–centroid distances = 3.556 (1)–3.716 (1) Å].

CCDC reference: 984236

Related literature

For background to piperazine derivatives, see: Tian et al. (2011 ); Stauffer (2011 ). For the preparation, see: Ghosh et al. (2010 ). For a similar structure, see: Shao et al. (2012 ).

Experimental

Crystal data

C₁₅H₁₉N₃O₂
M_r = 273.33
Triclinic, $[P \overline 1]$
a = 6.9537 (12) Å
b = 8.4410 (15) Å
c = 12.563 (2) Å
α = 96.260 (4)°
β = 98.381 (4)°
γ = 92.647 (3)°
V = 723.7 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.30 × 0.28 × 0.25 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2000 ) T_min = 0.975, T_max = 0.979
4194 measured reflections
2654 independent reflections
2206 reflections with I > 2σ(I)
R_int = 0.022

Refinement

R[F² > 2σ(F²)] = 0.047
wR(F²) = 0.154
S = 1.01
2654 reflections
183 parameters
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯O1ⁱ	0.93	2.57	3.406 (3)	149
C15—H15B⋯O2ⁱⁱ	0.96	2.53	3.343 (3)	142
Symmetry codes: (i) x, y-1, z; (ii) -x+1, -y, -z.

Data collection: APEX2 (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

CCDC reference: 984236

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: 10.1107/S1600536814002232/hb7071sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536814002232/hb7071Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536814002232/hb7071Isup3.cdx

Supporting information file. DOI: 10.1107/S1600536814002232/hb7071Isup4.cml

checkCIF report

Comment top

Piperazine derivatives have received much attention for their pharmaceutical activities (Tian, et al., 2011; Stauffer, 2011). The title compound was synthesized from N-(2-bromoethyl)phthalimide and N-methylpiperazine (Ghosh, et al., 2010), as a drug intermediate. In the molecule, Fig. 1, the six-membered piperazine ring adopts the chair conformation. The phthalimide ring is coplanar [r.m.s. deviations = 0.01 Å]. In the crystal, Fig. 2, molecules are linked via intermolecular C–H···O hydrogen bonding interactions (Table 1) and π···π stacking interactions involving the benzene and maleinimide rings (Table 2), which is different form the similar compound (Shao, et al., 2012).

Related literature top

For background to piperazine derivatives, see: Tian et al. (2011); Stauffer (2011). For the preparation, see: Ghosh et al. (2010). For a similar structure, see: Shao et al. (2012).

Experimental top

A suspension of N-(2-bromoethyl)phthalimide (2.54 g, 10.0 mmol), N-methylpiperazine (1.10 g, 11.1 mmol) and K₂CO₃ (2.70 g, 19.6 mmol) in 20 ml CH₃CN was stirred at room temperature for 0.5 h, and then heated to reflux for over 20 h. After cooling and filtration, the filter residue was washed with CH₃CN. And the filtrate and washing were combined prior to removing the solvent under vacuum. The title compound (2.15 g, 7.9 mmol) was obtained as colorless needles with m.p. 102.2–103.0 °C, after recrystallization from n-hexane. Colourless blocks were obtained by slow evaporation of CH₃OH.

Computing details top

Data collection: APEX2 (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. View of the title compound, showing 50% probability ellipsoids.
	Fig. 2. Perspective view of the title compound along a direction. Labels of atoms have been omitted for clarity.

2-[2-(4-Methylpiperazin-1-yl)ethyl]isoindoline-1,3-dione top

Crystal data top

C₁₅H₁₉N₃O₂	Z = 2
M_r = 273.33	F(000) = 292
Triclinic, P1	D_x = 1.254 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.9537 (12) Å	Cell parameters from 2417 reflections
b = 8.4410 (15) Å	θ = 2.8–29.0°
c = 12.563 (2) Å	µ = 0.09 mm⁻¹
α = 96.260 (4)°	T = 296 K
β = 98.381 (4)°	Block, colorless
γ = 92.647 (3)°	0.30 × 0.28 × 0.25 mm
V = 723.7 (2) Å³

Data collection top

Bruker APEXII CCD diffractometer	2654 independent reflections
Radiation source: fine-focus sealed tube	2206 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.022
φ and ω scans	θ_max = 25.5°, θ_min = 1.7°
Absorption correction: multi-scan (SADABS; Bruker, 2000)	h = −8→8
T_min = 0.975, T_max = 0.979	k = −10→9
4194 measured reflections	l = −7→15

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.047	H-atom parameters constrained
wR(F²) = 0.154	w = 1/[σ²(F_o²) + (0.0987P)² + 0.097P] where P = (F_o² + 2F_c²)/3
S = 1.01	(Δ/σ)_max < 0.001
2654 reflections	Δρ_max = 0.17 e Å⁻³
183 parameters	Δρ_min = −0.18 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.074 (13)

Crystal data top

C₁₅H₁₉N₃O₂	γ = 92.647 (3)°
M_r = 273.33	V = 723.7 (2) Å³
Triclinic, P1	Z = 2
a = 6.9537 (12) Å	Mo Kα radiation
b = 8.4410 (15) Å	µ = 0.09 mm⁻¹
c = 12.563 (2) Å	T = 296 K
α = 96.260 (4)°	0.30 × 0.28 × 0.25 mm
β = 98.381 (4)°

Data collection top

Bruker APEXII CCD diffractometer	2654 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2000)	2206 reflections with I > 2σ(I)
T_min = 0.975, T_max = 0.979	R_int = 0.022
4194 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.047	0 restraints
wR(F²) = 0.154	H-atom parameters constrained
S = 1.01	Δρ_max = 0.17 e Å⁻³
2654 reflections	Δρ_min = −0.18 e Å⁻³
183 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
C1	0.7472 (2)	0.1040 (2)	0.64462 (16)	0.0663 (5)
H1	0.7495	0.1864	0.7004	0.080*
C2	0.7384 (3)	−0.0535 (3)	0.6639 (2)	0.0853 (7)
H2	0.7335	−0.0780	0.7339	0.102*
C3	0.7366 (3)	−0.1743 (3)	0.5820 (3)	0.0952 (9)
H3	0.7321	−0.2795	0.5976	0.114*
C4	0.7415 (3)	−0.1437 (2)	0.4756 (2)	0.0866 (8)
H4	0.7398	−0.2263	0.4200	0.104*
C5	0.7489 (2)	0.0147 (2)	0.45574 (15)	0.0583 (5)
C6	0.75250 (19)	0.13529 (18)	0.53922 (13)	0.0490 (4)
C7	0.7637 (2)	0.28929 (18)	0.49368 (12)	0.0470 (4)
C8	0.7547 (2)	0.0895 (2)	0.35403 (15)	0.0623 (5)
C9	0.7949 (2)	0.3733 (3)	0.31185 (14)	0.0682 (5)
H9A	0.8471	0.3229	0.2500	0.082*
H9B	0.8920	0.4539	0.3501	0.082*
C10	0.6130 (3)	0.4551 (2)	0.27092 (14)	0.0618 (5)
H10A	0.5547	0.4975	0.3328	0.074*
H10B	0.6512	0.5447	0.2348	0.074*
C11	0.5329 (2)	0.3035 (2)	0.09326 (13)	0.0585 (4)
H11A	0.6436	0.2385	0.1059	0.070*
H11B	0.5750	0.3973	0.0624	0.070*
C12	0.3737 (3)	0.2097 (2)	0.01439 (13)	0.0613 (5)
H12A	0.4212	0.1801	−0.0534	0.074*
H12B	0.3373	0.1124	0.0431	0.074*
C13	0.1346 (2)	0.3462 (2)	0.09674 (13)	0.0534 (4)
H13A	0.0968	0.2504	0.1267	0.064*
H13B	0.0211	0.4083	0.0848	0.064*
C14	0.2917 (2)	0.44238 (19)	0.17559 (12)	0.0532 (4)
H14A	0.3254	0.5402	0.1467	0.064*
H14B	0.2430	0.4712	0.2432	0.064*
C15	0.0515 (3)	0.2147 (3)	−0.08443 (17)	0.0777 (6)
H15A	0.0143	0.1167	−0.0585	0.117*
H15B	0.0996	0.1915	−0.1519	0.117*
H15C	−0.0595	0.2779	−0.0951	0.117*
N1	0.46613 (18)	0.35309 (15)	0.19655 (9)	0.0484 (3)
N2	0.20302 (19)	0.30264 (16)	−0.00548 (10)	0.0541 (4)
N3	0.76325 (17)	0.25325 (17)	0.38367 (10)	0.0521 (4)
O1	0.77364 (19)	0.42351 (14)	0.54040 (10)	0.0671 (4)
O2	0.7541 (2)	0.0268 (2)	0.26330 (12)	0.0968 (6)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0513 (9)	0.0830 (13)	0.0639 (11)	0.0043 (8)	−0.0028 (8)	0.0210 (9)
C2	0.0537 (11)	0.0913 (16)	0.1136 (18)	0.0011 (10)	−0.0070 (11)	0.0526 (15)
C3	0.0492 (11)	0.0704 (14)	0.164 (3)	0.0016 (9)	−0.0154 (13)	0.0502 (17)
C4	0.0445 (9)	0.0536 (11)	0.149 (2)	0.0062 (7)	−0.0133 (11)	−0.0109 (12)
C5	0.0338 (7)	0.0555 (9)	0.0795 (12)	0.0077 (6)	−0.0046 (7)	−0.0040 (8)
C6	0.0329 (7)	0.0546 (9)	0.0564 (9)	0.0042 (6)	−0.0025 (6)	0.0048 (7)
C7	0.0382 (7)	0.0555 (9)	0.0436 (8)	0.0009 (6)	−0.0003 (6)	−0.0014 (6)
C8	0.0384 (8)	0.0796 (12)	0.0612 (10)	0.0113 (7)	0.0005 (7)	−0.0197 (8)
C9	0.0503 (9)	0.1015 (14)	0.0504 (9)	−0.0138 (9)	0.0030 (7)	0.0131 (9)
C10	0.0672 (10)	0.0666 (10)	0.0485 (9)	−0.0100 (8)	0.0004 (7)	0.0109 (7)
C11	0.0535 (9)	0.0802 (11)	0.0439 (8)	0.0120 (8)	0.0104 (7)	0.0087 (8)
C12	0.0636 (10)	0.0726 (11)	0.0466 (9)	0.0210 (8)	0.0065 (7)	−0.0027 (8)
C13	0.0515 (9)	0.0584 (9)	0.0511 (9)	0.0121 (7)	0.0080 (7)	0.0067 (7)
C14	0.0598 (9)	0.0564 (9)	0.0442 (8)	0.0118 (7)	0.0090 (7)	0.0040 (7)
C15	0.0771 (13)	0.0777 (13)	0.0673 (12)	0.0170 (10)	−0.0150 (10)	−0.0104 (10)
N1	0.0503 (7)	0.0565 (8)	0.0385 (7)	0.0033 (5)	0.0062 (5)	0.0066 (5)
N2	0.0588 (8)	0.0588 (8)	0.0423 (7)	0.0119 (6)	0.0009 (6)	0.0015 (6)
N3	0.0424 (7)	0.0677 (9)	0.0434 (7)	0.0035 (5)	0.0020 (5)	−0.0005 (6)
O1	0.0850 (9)	0.0542 (7)	0.0564 (7)	0.0002 (6)	0.0027 (6)	−0.0058 (5)
O2	0.0825 (10)	0.1228 (13)	0.0717 (9)	0.0219 (9)	0.0034 (7)	−0.0439 (9)

Geometric parameters (Å, º) top

C1—C2	1.377 (3)	C10—H10A	0.9700
C1—C6	1.384 (3)	C10—H10B	0.9700
C1—H1	0.9300	C11—N1	1.466 (2)
C2—C3	1.366 (4)	C11—C12	1.504 (2)
C2—H2	0.9300	C11—H11A	0.9700
C3—C4	1.394 (4)	C11—H11B	0.9700
C3—H3	0.9300	C12—N2	1.459 (2)
C4—C5	1.386 (3)	C12—H12A	0.9700
C4—H4	0.9300	C12—H12B	0.9700
C5—C6	1.376 (2)	C13—N2	1.450 (2)
C5—C8	1.490 (3)	C13—C14	1.503 (2)
C6—C7	1.480 (2)	C13—H13A	0.9700
C7—O1	1.2120 (19)	C13—H13B	0.9700
C7—N3	1.382 (2)	C14—N1	1.464 (2)
C8—O2	1.202 (2)	C14—H14A	0.9700
C8—N3	1.388 (2)	C14—H14B	0.9700
C9—N3	1.458 (2)	C15—N2	1.451 (2)
C9—C10	1.519 (3)	C15—H15A	0.9600
C9—H9A	0.9700	C15—H15B	0.9600
C9—H9B	0.9700	C15—H15C	0.9600
C10—N1	1.457 (2)

C2—C1—C6	117.6 (2)	C12—C11—H11A	109.4
C2—C1—H1	121.2	N1—C11—H11B	109.4
C6—C1—H1	121.2	C12—C11—H11B	109.4
C3—C2—C1	121.1 (2)	H11A—C11—H11B	108.0
C3—C2—H2	119.4	N2—C12—C11	111.05 (14)
C1—C2—H2	119.4	N2—C12—H12A	109.4
C2—C3—C4	121.6 (2)	C11—C12—H12A	109.4
C2—C3—H3	119.2	N2—C12—H12B	109.4
C4—C3—H3	119.2	C11—C12—H12B	109.4
C5—C4—C3	117.5 (2)	H12A—C12—H12B	108.0
C5—C4—H4	121.3	N2—C13—C14	110.46 (13)
C3—C4—H4	121.3	N2—C13—H13A	109.6
C6—C5—C4	120.36 (19)	C14—C13—H13A	109.6
C6—C5—C8	107.93 (15)	N2—C13—H13B	109.6
C4—C5—C8	131.71 (19)	C14—C13—H13B	109.6
C5—C6—C1	121.86 (17)	H13A—C13—H13B	108.1
C5—C6—C7	107.87 (15)	N1—C14—C13	111.53 (13)
C1—C6—C7	130.27 (15)	N1—C14—H14A	109.3
O1—C7—N3	124.58 (15)	C13—C14—H14A	109.3
O1—C7—C6	128.68 (14)	N1—C14—H14B	109.3
N3—C7—C6	106.73 (13)	C13—C14—H14B	109.3
O2—C8—N3	124.7 (2)	H14A—C14—H14B	108.0
O2—C8—C5	129.28 (19)	N2—C15—H15A	109.5
N3—C8—C5	106.01 (14)	N2—C15—H15B	109.5
N3—C9—C10	114.32 (13)	H15A—C15—H15B	109.5
N3—C9—H9A	108.7	N2—C15—H15C	109.5
C10—C9—H9A	108.7	H15A—C15—H15C	109.5
N3—C9—H9B	108.7	H15B—C15—H15C	109.5
C10—C9—H9B	108.7	C10—N1—C14	108.35 (13)
H9A—C9—H9B	107.6	C10—N1—C11	112.08 (13)
N1—C10—C9	114.94 (15)	C14—N1—C11	108.84 (12)
N1—C10—H10A	108.5	C13—N2—C15	111.53 (14)
C9—C10—H10A	108.5	C13—N2—C12	108.61 (12)
N1—C10—H10B	108.5	C15—N2—C12	111.25 (13)
C9—C10—H10B	108.5	C7—N3—C8	111.45 (15)
H10A—C10—H10B	107.5	C7—N3—C9	123.36 (15)
N1—C11—C12	111.26 (13)	C8—N3—C9	124.69 (15)
N1—C11—H11A	109.4

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3···O1ⁱ	0.93	2.57	3.406 (3)	149
C15—H15B···O2ⁱⁱ	0.96	2.53	3.343 (3)	142

Symmetry codes: (i) x, y−1, z; (ii) −x+1, −y, −z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3···O1ⁱ	0.93	2.57	3.406 (3)	149
C15—H15B···O2ⁱⁱ	0.96	2.53	3.343 (3)	142

Symmetry codes: (i) x, y−1, z; (ii) −x+1, −y, −z.

Table 2 π-π hydrogen-bond geometry (Å) top

CgI	CgJ	CgI···CgJ
Cg1	Cg3ⁱ	3.607 (1)
Cg1	Cg3ⁱⁱ	3.716 (1)
Cg1	Cg3ⁱ	3.556 (1)

Symmetry codes: (i) 1-x, -y, 1-z; (ii) 2-x, -y, 1-z; Cg1 and Cg3 are the centroids of the N3–C7–C6–C5–C8 and C1–C6 rings.

Acknowledgements

We gratefully acknowledge the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and the Natural Science Foundation of Jiangsu Education Department (No. SCZ1212400004) for financial support.

References

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