4-Chloro-N-(isoquinolin-3-yl)butanamide

Loganathan, C.; Ananad, S.A.A.; Alphonsa, A.T.; Kabilan, S.; Selvanayagam, S.

doi:10.1107/S2414314616012906

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 1| Part 8| August 2016| x161290

doi:10.1107/S2414314616012906

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access

4-Chloro-N-(isoquinolin-3-yl)butanamide

C. Loganathan,^a S. Athavan Alias Ananad,^a A. Therasa Alphonsa,^a S. Kabilan ^a ^* and S. Selvanayagam ^b ‡

^aDrug Discovery Lab, Department of Chemistry, Annamalai University, Annamalainagar, Chidambaram 608 002, India, and ^bPG & Research Department of Physics, Government Arts College, Melur 625 106, India
^*Correspondence e-mail: profskabilan@gmail.com

Edited by M. Bolte, Goethe-Universität Frankfurt Germany (Received 12 July 2016; accepted 9 August 2016; online 12 August 2016)

All C, N and O atoms of the title compound, C₁₃H₁₃ClN₂O, lie in a common plane (r.m.s. deviation = 0.096 Å). The Cl atom deviates by 0.940 (3) Å from this plane. In the crystal, molecules are linked via N—H⋯N and C—H⋯O hydrogen bonds which form R₂²(8) and R₂²(16) graph-set dimers. In addition, molecules are linked via C—H⋯O intermolecular interactions which form C(4) chains propagating along the [100] direction of the unit cell.

Keywords: crystal structure; isoquinoline derivatives; anticancer agnet; N—H⋯N and C—H⋯O hydrogen bonds.

CCDC reference: 1498471

Structure description

Isoquinoline derivatives act as potential phosphodiesterase type 4 (PDE4) and histone deacetylase inhibitors (Song et al., 2015 ; Yang et al., 2015a ). These derivatives act as anticancer agents (Yang et al., 2015b ). In view of the interesting applications of isoquinoline derivatives, we synthesized the title compound and report herein its crystal structure. The molecular structure of the title compound is illustrated in Fig. 1.

Figure 1
The molecular structure of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 30% probability level.

All C, N and O atoms lie in a common plane (r.m.s. deviation = 0.096 Å). The Cl atom deviates by 0.940 (3) Å from this plane.

The molecular structure is influenced by intramolecular C—H⋯O interactions (Table 1). In the crystal, N—H⋯N and C—H⋯O intermolecular hydrogen bonds link the molecules, forming $[R_{2}^{2}]$ (8) and $[R_{2}^{2}]$ (16) graph-set dimers in the unit cell (Fig. 2). In addition, C—H⋯O intermolecular interactions link the molecules, forming C(4) chains propagating along the [100] plane of the unit cell (Fig. 3).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C8—H8⋯O1	0.93	2.27	2.863 (4)	121
N2—H2⋯N1ⁱ	0.86	2.50	3.348 (4)	169
C6—H6⋯O1ⁱⁱ	0.93	2.58	3.475 (4)	161
C11—H11A⋯O1ⁱⁱⁱ	0.97	2.56	3.503 (4)	163
Symmetry codes: (i) -x, -y, -z; (ii) -x+1, -y+1, -z; (iii) x-1, y, z.

Figure 2
The crystal packing of the title compound, viewed down the a axis. N—H⋯N and C—H⋯O hydrogen bonds are shown as dashed lines (see Table 1

). For clarity, H atoms not involved in these hydrogen bonds have been omitted.

Figure 3
The packing of the title compound, showing C—H⋯O interactions as dashed lines forming C(4) chain. For clarity, H atoms not involved in these interactions have been omitted.

Synthesis and crystallization

To a stirred solution of 3-aminoisoquinoline (1 g, 1 equivalent) in dichloromethane (10 ml), 1.5 equivalents of pyridine (0.82 g) were added and allowed to stir for 20 min. The reaction mixture was cooled to 273 K. Then, 1.1 equivalents of chlorobutyryl chloride (1.07 g) were added dropwise to the reaction mass over a period of 5 min. The reaction mass was warmed to room temperature and stirring was continued for 90 min. Upon completion of the reaction, the reaction mass was quenched with water and extracted with dichloromethane. The organic layer was further washed with 10% sodium bicarbonate solution (10 ml), and 1 N HCl (10 ml) was added to the organic layer, which was dried over sodium sulfate and concentrated under reduced pressure. The crude product was triturated with dichloromethane–hexane to yield 1.2 g (69.7%) of the pure product of the title compound. The solid was further recrystallized from ethanol to yield a diffraction-quality crystal of the title compound.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₃H₁₃ClN₂O
M_r	248.70
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	293
a, b, c (Å)	5.263 (3), 9.782 (5), 12.795 (6)
α, β, γ (°)	78.591 (9), 80.188 (7), 74.418 (10)
V (Å³)	617.2 (5)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.29
Crystal size (mm)	0.40 × 0.20 × 0.20

Data collection
Diffractometer	Rigaku Saturn724+ area-dectector
No. of measured, independent and observed [I > 2σ(I)] reflections	3534, 2746, 1546
R_int	0.124
(sin θ/λ)_max (Å⁻¹)	0.653

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.069, 0.227, 1.01
No. of reflections	2746
No. of parameters	154
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.51
Computer programs: CrystalClear SM-Expert (Rigaku, 2011 ), SHELXS97 (Sheldrick, 2008 ), ORTEP-3 for Windows (Farrugia, 2012 ), SHELXL2014 (Sheldrick, 2015 ) and PLATON (Spek, 2009 ).

Structural data

CCDC reference: 1498471

Crystal structure: contains datablocks I, global. DOI: 10.1107/S2414314616012906/bt4019sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S2414314616012906/bt4019Isup2.hkl

Supporting information file. DOI: 10.1107/S2414314616012906/bt4019Isup3.cml

checkCIF report

Computing details top

Data collection: CrystalClear SM-Expert (Rigaku, 2011); cell refinement: CrystalClear SM-Expert (Rigaku, 2011); data reduction: CrystalClear SM-Expert (Rigaku, 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2009).

4-Chloro-N-(isoquinolin-3-yl)butanamide top

Crystal data top

C₁₃H₁₃ClN₂O	Z = 2
M_r = 248.70	F(000) = 260
Triclinic, P1	D_x = 1.338 Mg m⁻³
a = 5.263 (3) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.782 (5) Å	Cell parameters from 2288 reflections
c = 12.795 (6) Å	θ = 3.2–26.8°
α = 78.591 (9)°	µ = 0.29 mm⁻¹
β = 80.188 (7)°	T = 293 K
γ = 74.418 (10)°	Prism, colourless
V = 617.2 (5) Å³	0.40 × 0.20 × 0.20 mm

Data collection top

Rigaku Saturn724+ area-dectector diffractometer	R_int = 0.124
Radiation source: fine-focus sealed tube	θ_max = 27.7°, θ_min = 3.3°
ω scans	h = −6→6
3534 measured reflections	k = −12→8
2746 independent reflections	l = −16→11
1546 reflections with I > 2σ(I)

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.069	H-atom parameters constrained
wR(F²) = 0.227	w = 1/[σ²(F_o²) + (0.1016P)²] where P = (F_o² + 2F_c²)/3
S = 1.01	(Δ/σ)_max < 0.001
2746 reflections	Δρ_max = 0.20 e Å⁻³
154 parameters	Δρ_min = −0.51 e Å⁻³

Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	−0.2114 (2)	0.32757 (11)	−0.44065 (7)	0.0864 (4)
O1	0.2508 (5)	0.3932 (2)	−0.12457 (19)	0.0706 (7)
N1	0.2207 (5)	0.0212 (3)	0.10506 (19)	0.0479 (6)
N2	0.1134 (5)	0.1921 (3)	−0.04217 (18)	0.0504 (6)
H2	0.0160	0.1372	−0.0488	0.060*
C1	0.3335 (6)	−0.0247 (3)	0.1944 (3)	0.0544 (8)
H1	0.3133	−0.1125	0.2340	0.065*
C2	0.4829 (6)	0.0498 (3)	0.2343 (2)	0.0490 (7)
C3	0.5944 (7)	−0.0020 (4)	0.3322 (3)	0.0592 (8)
H3	0.5702	−0.0884	0.3731	0.071*
C4	0.7372 (7)	0.0742 (4)	0.3668 (3)	0.0668 (9)
H4	0.8106	0.0394	0.4309	0.080*
C5	0.7737 (7)	0.2064 (4)	0.3051 (3)	0.0617 (9)
H5	0.8722	0.2573	0.3291	0.074*
C6	0.6667 (6)	0.2599 (3)	0.2112 (3)	0.0554 (8)
H6	0.6923	0.3468	0.1717	0.066*
C7	0.5160 (6)	0.1831 (3)	0.1737 (2)	0.0477 (7)
C8	0.3925 (6)	0.2331 (3)	0.0787 (2)	0.0497 (7)
H8	0.4076	0.3205	0.0369	0.060*
C9	0.2501 (5)	0.1512 (3)	0.0488 (2)	0.0446 (7)
C10	0.1164 (6)	0.3077 (3)	−0.1209 (2)	0.0485 (7)
C11	−0.0623 (6)	0.3197 (3)	−0.2049 (2)	0.0557 (8)
H11A	−0.2423	0.3243	−0.1698	0.067*
H11B	−0.0044	0.2336	−0.2381	0.067*
C12	−0.0639 (6)	0.4503 (3)	−0.2919 (3)	0.0585 (8)
H12A	−0.0974	0.5352	−0.2583	0.070*
H12B	0.1103	0.4391	−0.3338	0.070*
C13	−0.2694 (7)	0.4728 (4)	−0.3661 (3)	0.0643 (9)
H13A	−0.2698	0.5615	−0.4161	0.077*
H13B	−0.4435	0.4831	−0.3243	0.077*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.1257 (10)	0.0752 (7)	0.0648 (6)	−0.0301 (6)	−0.0284 (6)	−0.0042 (5)
O1	0.0827 (17)	0.0644 (15)	0.0754 (15)	−0.0452 (13)	−0.0274 (13)	0.0170 (12)
N1	0.0511 (14)	0.0387 (13)	0.0539 (14)	−0.0145 (11)	−0.0064 (11)	−0.0026 (10)
N2	0.0528 (15)	0.0450 (14)	0.0557 (14)	−0.0218 (11)	−0.0103 (11)	0.0032 (11)
C1	0.0579 (19)	0.0437 (17)	0.0635 (19)	−0.0212 (14)	−0.0089 (15)	0.0002 (13)
C2	0.0531 (18)	0.0396 (16)	0.0554 (17)	−0.0136 (13)	−0.0060 (13)	−0.0079 (12)
C3	0.066 (2)	0.0543 (19)	0.0581 (19)	−0.0200 (16)	−0.0130 (15)	0.0008 (14)
C4	0.077 (2)	0.067 (2)	0.063 (2)	−0.0202 (18)	−0.0255 (17)	−0.0069 (17)
C5	0.068 (2)	0.057 (2)	0.068 (2)	−0.0229 (17)	−0.0087 (16)	−0.0199 (16)
C6	0.062 (2)	0.0465 (17)	0.0624 (19)	−0.0196 (15)	−0.0059 (15)	−0.0126 (14)
C7	0.0435 (16)	0.0436 (16)	0.0571 (17)	−0.0128 (13)	−0.0006 (13)	−0.0120 (13)
C8	0.0557 (18)	0.0409 (16)	0.0548 (17)	−0.0193 (14)	−0.0040 (13)	−0.0053 (12)
C9	0.0443 (16)	0.0397 (15)	0.0485 (15)	−0.0135 (12)	0.0003 (12)	−0.0047 (11)
C10	0.0511 (17)	0.0450 (16)	0.0516 (16)	−0.0205 (13)	−0.0084 (12)	0.0007 (12)
C11	0.0577 (19)	0.0545 (18)	0.0604 (18)	−0.0265 (15)	−0.0130 (14)	0.0011 (14)
C12	0.058 (2)	0.0500 (18)	0.068 (2)	−0.0219 (15)	−0.0162 (15)	0.0065 (14)
C13	0.069 (2)	0.0540 (19)	0.070 (2)	−0.0187 (17)	−0.0199 (17)	0.0055 (15)

Geometric parameters (Å, º) top

Cl1—C13	1.796 (4)	C5—H5	0.9300
O1—C10	1.222 (3)	C6—C7	1.420 (4)
N1—C1	1.321 (4)	C6—H6	0.9300
N1—C9	1.366 (3)	C7—C8	1.415 (4)
N2—C10	1.359 (3)	C8—C9	1.375 (4)
N2—C9	1.407 (4)	C8—H8	0.9300
N2—H2	0.8600	C10—C11	1.513 (4)
C1—C2	1.415 (4)	C11—C12	1.520 (4)
C1—H1	0.9300	C11—H11A	0.9700
C2—C7	1.417 (4)	C11—H11B	0.9700
C2—C3	1.418 (4)	C12—C13	1.503 (4)
C3—C4	1.364 (4)	C12—H12A	0.9700
C3—H3	0.9300	C12—H12B	0.9700
C4—C5	1.418 (5)	C13—H13A	0.9700
C4—H4	0.9300	C13—H13B	0.9700
C5—C6	1.363 (5)

C1—N1—C9	116.6 (2)	C9—C8—H8	120.3
C10—N2—C9	128.0 (2)	C7—C8—H8	120.3
C10—N2—H2	116.0	N1—C9—C8	124.0 (3)
C9—N2—H2	116.0	N1—C9—N2	111.8 (2)
N1—C1—C2	124.9 (3)	C8—C9—N2	124.2 (3)
N1—C1—H1	117.5	O1—C10—N2	123.8 (3)
C2—C1—H1	117.5	O1—C10—C11	123.0 (2)
C1—C2—C7	117.7 (3)	N2—C10—C11	113.2 (2)
C1—C2—C3	122.9 (3)	C10—C11—C12	113.4 (2)
C7—C2—C3	119.5 (3)	C10—C11—H11A	108.9
C4—C3—C2	120.4 (3)	C12—C11—H11A	108.9
C4—C3—H3	119.8	C10—C11—H11B	108.9
C2—C3—H3	119.8	C12—C11—H11B	108.9
C3—C4—C5	120.1 (3)	H11A—C11—H11B	107.7
C3—C4—H4	120.0	C13—C12—C11	113.1 (3)
C5—C4—H4	120.0	C13—C12—H12A	109.0
C6—C5—C4	121.0 (3)	C11—C12—H12A	109.0
C6—C5—H5	119.5	C13—C12—H12B	109.0
C4—C5—H5	119.5	C11—C12—H12B	109.0
C5—C6—C7	120.1 (3)	H12A—C12—H12B	107.8
C5—C6—H6	120.0	C12—C13—Cl1	112.8 (2)
C7—C6—H6	120.0	C12—C13—H13A	109.0
C8—C7—C2	117.4 (3)	Cl1—C13—H13A	109.0
C8—C7—C6	123.6 (3)	C12—C13—H13B	109.0
C2—C7—C6	119.0 (3)	Cl1—C13—H13B	109.0
C9—C8—C7	119.4 (3)	H13A—C13—H13B	107.8

C9—N1—C1—C2	−0.8 (5)	C2—C7—C8—C9	−0.7 (4)
N1—C1—C2—C7	−0.5 (5)	C6—C7—C8—C9	−179.9 (3)
N1—C1—C2—C3	178.3 (3)	C1—N1—C9—C8	1.4 (4)
C1—C2—C3—C4	179.9 (3)	C1—N1—C9—N2	−177.6 (2)
C7—C2—C3—C4	−1.3 (5)	C7—C8—C9—N1	−0.7 (4)
C2—C3—C4—C5	0.3 (5)	C7—C8—C9—N2	178.2 (2)
C3—C4—C5—C6	0.4 (6)	C10—N2—C9—N1	−174.0 (3)
C4—C5—C6—C7	−0.1 (5)	C10—N2—C9—C8	7.0 (5)
C1—C2—C7—C8	1.2 (4)	C9—N2—C10—O1	2.2 (5)
C3—C2—C7—C8	−177.6 (3)	C9—N2—C10—C11	−178.3 (3)
C1—C2—C7—C6	−179.5 (3)	O1—C10—C11—C12	−1.7 (5)
C3—C2—C7—C6	1.6 (4)	N2—C10—C11—C12	178.9 (3)
C5—C6—C7—C8	178.2 (3)	C10—C11—C12—C13	−172.0 (3)
C5—C6—C7—C2	−1.0 (5)	C11—C12—C13—Cl1	−63.1 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C8—H8···O1	0.93	2.27	2.863 (4)	121
N2—H2···N1ⁱ	0.86	2.50	3.348 (4)	169
C6—H6···O1ⁱⁱ	0.93	2.58	3.475 (4)	161
C11—H11A···O1ⁱⁱⁱ	0.97	2.56	3.503 (4)	163

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

Footnotes

‡Additional correspondence author: s_selvanayagam@rediffmail.com

References

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4-Chloro-N-(isoquinolin-3-yl)butanamide

Structure description

Synthesis and crystallization

Refinement

Structural data

Footnotes

References

organic compounds