7-Chloro-1,2-dihydro­furo[2,3-c]isoquinolin-5-amine

Okuda, K.; Hirota, T.; Sasaki, K.; Ishida, H.

doi:10.1107/S160053681004273X

organic compounds

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ISSN: 2056-9890

Volume 66| Part 11| November 2010| Page o2949

https://doi.org/10.1107/S160053681004273X

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7-Chloro-1,2-dihydrofuro[2,3-c]isoquinolin-5-amine

Kensuke Okuda,^a ^* Takashi Hirota,^b Kenji Sasaki ^b and Hiroyuki Ishida ^c ^*

^aLaboratory of Medicinal and Pharmaceutical Chemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan, ^bFaculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan, and ^cDepartment of Chemistry, Faculty of Science, Okayama University, Okayama 700-8530, Japan
^*Correspondence e-mail: okuda@gifu-pu.ac.jp, ishidah@cc.okayama-u.ac.jp

(Received 19 October 2010; accepted 21 October 2010; online 30 October 2010)

In the title compound, C₁₁H₉ClN₂O, the fused-ring system is essentially planar, with a maximum deviation of 0.0323 (16) Å. In the crystal, molecules are connected by N—H⋯O hydrogen bonds forming a zigzag chain along the c axis. Molecules are further stacked along the a axis through weak π–π interactions, the shortest distance between ring centroids being 3.6476 (8) Å.

Related literature

For background to this work and the synthesis of the title compound, see: Okuda et al. (2010 ).

Experimental

Crystal data

C₁₁H₉ClN₂O
M_r = 220.66
Orthorhombic, P n a 2₁
a = 7.2948 (6) Å
b = 12.0703 (11) Å
c = 10.8869 (8) Å
V = 958.60 (14) Å³
Z = 4
Mo Kα radiation
μ = 0.37 mm⁻¹
T = 200 K
0.40 × 0.25 × 0.08 mm

Data collection

Rigaku R-AXIS RAPID II diffractometer
Absorption correction: numerical (NUMABS; Higashi, 1999 ) T_min = 0.896, T_max = 0.971
11594 measured reflections
2776 independent reflections
2531 reflections with I > 2σ(I)
R_int = 0.016

Refinement

R[F² > 2σ(F²)] = 0.031
wR(F²) = 0.083
S = 1.11
2776 reflections
144 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.42 e Å⁻³
Δρ_min = −0.17 e Å⁻³
Absolute structure: Flack (1983 ), 1311 Friedel pairs
Flack parameter: −0.02 (5)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯O1ⁱ	0.82 (2)	2.43 (2)	3.062 (2)	134 (2)
Symmetry code: (i) $[-x+1, -y+1, z+{\script{1\over 2}}]$ .

Data collection: PROCESS-AUTO (Rigaku/MSC, 2004 ); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997 ); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2004) and PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S160053681004273X/gk2312sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S160053681004273X/gk2312Isup2.hkl

checkCIF report

Comment top

As an extension of our work to develop complex heterocyclic skeletons for potential pharmaceutics in one step using Truce-Smiles rearrangement, we got interested in the reaction of 2-(3-cyanopropoxy)benzonitriles with bases (Okuda et al., 2010). As is well established, the key step of the Truce-Smiles rearrangement is the ipso attack of an incoming nucleophile. So electron withdrawing chlorine atom at 5-position seemed to be favorable for this rearrangement reaction. The product, 7-chloro-1,2-dihydrofuro[2,3-c]isoquinolin-5-amine, was obtained in 83% yield, which was higher than the product yield of 1,2-dihydrofuro[2,3-c]isoquinolin-5-amine (60%) from 5-unsubsituted starting material as we had assumed.

In the title compound, C₁₁H₉ClN₂O, the fused three-ring system is essentially planar with a maximum deviation of 0.0323 (16) Å at atom C4. In the crystal structure, the molecules are connected by an N—H···O hydrogen bond, forming a zigzag chain along the c axis. The molecules are further stacked along the a axis through weak π–π interactions between the isoquinoline ring systems [Cg1···Cg1 (-1/2 + x, 3/2 - y, z) = 4.0137 (8) Å, Cg1···Cg2 (1/2 + x, 3/2 - y, z) = 3.6858 (8) Å and Cg2···Cg2 (1/2 + x, 3/2 - y, z) = 3.6476 (8) Å; Cg1 and Cg2 are the centroids of N1/C1/C11/C6/C5/C2 and C6–C11 rings, respectively.]

Related literature top

For background to this work and the synthesis of the title compound, see: Okuda et al. (2010).

Experimental top

Detailed experimental procedure of the synthesis of 7-chloro-1,2-dihydrofuro[2,3-c]isoquinolin-5-amine (m.p. 527–528 K from ethyl acetate) from 5-chloro-2-(3-cyanopropoxy)benzonitrile was already described in our precedent report (Okuda et al., 2010). Single crystals suitable for X-ray diffraction were obtained from an ethyl acetate solution.

Structure description top

For background to this work and the synthesis of the title compound, see: Okuda et al. (2010).

Computing details top

Data collection: PROCESS-AUTO (Rigaku/MSC, 2004); cell refinement: PROCESS-AUTO (Rigaku/MSC, 2004); data reduction: CrystalStructure (Rigaku/MSC, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2004) and PLATON (Spek, 2009).

Figures top

	Fig. 1. The molecular structure of the title compound, with the atom-labeling. Displacement ellipsoids of non-H atoms are drawn at the 50% probability level.
	Fig. 2. A packing diagram of the title compound, showing a molecular chain running along the c axis. The dashed lines indicate N—H···O hydrogen bonds. C-bound H atoms have been omitted.

7-Chloro-1,2-dihydrofuro[2,3-c]isoquinolin-5-amine top

Crystal data top

C₁₁H₉ClN₂O	F(000) = 456.00
M_r = 220.66	D_x = 1.529 Mg m⁻³
Orthorhombic, Pna2₁	Mo Kα radiation, λ = 0.71075 Å
Hall symbol: P 2c -2n	Cell parameters from 10138 reflections
a = 7.2948 (6) Å	θ = 3.3–30.0°
b = 12.0703 (11) Å	µ = 0.37 mm⁻¹
c = 10.8869 (8) Å	T = 200 K
V = 958.60 (14) Å³	Platelet, yellow
Z = 4	0.40 × 0.25 × 0.08 mm

Data collection top

Rigaku R-AXIS RAPID II diffractometer	2531 reflections with I > 2σ(I)
Detector resolution: 10.00 pixels mm^-1	R_int = 0.016
ω scans	θ_max = 30.0°
Absorption correction: numerical (NUMABS; Higashi, 1999)	h = −10→9
T_min = 0.896, T_max = 0.971	k = −16→16
11594 measured reflections	l = −15→15
2776 independent reflections

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)] = 0.031	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.083	w = 1/[σ²(F_o²) + (0.056P)² + 0.0168P] where P = (F_o² + 2F_c²)/3
S = 1.11	(Δ/σ)_max = 0.001
2776 reflections	Δρ_max = 0.42 e Å⁻³
144 parameters	Δρ_min = −0.17 e Å⁻³
1 restraint	Absolute structure: Flack (1983), 1311 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.02 (5)

Crystal data top

C₁₁H₉ClN₂O	V = 958.60 (14) Å³
M_r = 220.66	Z = 4
Orthorhombic, Pna2₁	Mo Kα radiation
a = 7.2948 (6) Å	µ = 0.37 mm⁻¹
b = 12.0703 (11) Å	T = 200 K
c = 10.8869 (8) Å	0.40 × 0.25 × 0.08 mm

Data collection top

Rigaku R-AXIS RAPID II diffractometer	2776 independent reflections
Absorption correction: numerical (NUMABS; Higashi, 1999)	2531 reflections with I > 2σ(I)
T_min = 0.896, T_max = 0.971	R_int = 0.016
11594 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.031	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.083	Δρ_max = 0.42 e Å⁻³
S = 1.11	Δρ_min = −0.17 e Å⁻³
2776 reflections	Absolute structure: Flack (1983), 1311 Friedel pairs
144 parameters	Absolute structure parameter: −0.02 (5)
1 restraint

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
Cl1	0.20651 (5)	0.70539 (3)	0.83910 (3)	0.04205 (11)
O1	0.5523 (2)	0.71804 (10)	0.14408 (11)	0.0454 (3)
N1	0.49290 (17)	0.58990 (10)	0.29743 (12)	0.0364 (3)
N2	0.4320 (3)	0.46639 (12)	0.4512 (2)	0.0522 (4)
C1	0.44057 (18)	0.57365 (11)	0.41337 (13)	0.0328 (3)
C2	0.49833 (18)	0.69629 (12)	0.26182 (13)	0.0317 (3)
C3	0.5446 (2)	0.83764 (15)	0.12840 (14)	0.0431 (3)
H3A	0.4551	0.8569	0.0635	0.052*
H3B	0.6664	0.8662	0.1037	0.052*
C4	0.4862 (2)	0.88976 (13)	0.25161 (14)	0.0375 (3)
H4A	0.5839	0.9376	0.2858	0.045*
H4B	0.3720	0.9333	0.2430	0.045*
C5	0.45715 (16)	0.78864 (9)	0.32871 (13)	0.0267 (2)
C6	0.39999 (16)	0.77295 (10)	0.45094 (12)	0.0239 (2)
C7	0.35257 (17)	0.86096 (10)	0.53113 (12)	0.0279 (2)
H7	0.3619	0.9353	0.5030	0.033*
C8	0.29337 (17)	0.84059 (12)	0.64864 (12)	0.0302 (3)
H8	0.2602	0.9000	0.7013	0.036*
C9	0.28264 (17)	0.73061 (12)	0.68982 (13)	0.0297 (3)
C10	0.32916 (18)	0.64268 (11)	0.61666 (12)	0.0297 (3)
H10	0.3215	0.5692	0.6474	0.036*
C11	0.38839 (17)	0.66225 (10)	0.49559 (12)	0.0258 (2)
H2A	0.430 (3)	0.4520 (19)	0.525 (2)	0.054 (6)*
H2B	0.466 (4)	0.418 (2)	0.406 (2)	0.069 (8)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.04108 (18)	0.0588 (2)	0.02626 (15)	0.00458 (13)	0.00713 (15)	0.00747 (16)
O1	0.0576 (7)	0.0536 (7)	0.0249 (5)	0.0026 (5)	0.0091 (5)	−0.0055 (4)
N1	0.0402 (6)	0.0329 (6)	0.0361 (6)	0.0028 (4)	0.0018 (5)	−0.0093 (5)
N2	0.0730 (10)	0.0248 (6)	0.0588 (10)	0.0045 (6)	0.0114 (8)	−0.0006 (6)
C1	0.0332 (6)	0.0269 (6)	0.0382 (7)	0.0012 (5)	−0.0001 (5)	−0.0036 (5)
C2	0.0300 (6)	0.0396 (7)	0.0254 (6)	0.0021 (5)	0.0013 (5)	−0.0046 (5)
C3	0.0492 (8)	0.0533 (9)	0.0267 (6)	0.0020 (7)	0.0044 (6)	0.0073 (6)
C4	0.0435 (7)	0.0388 (7)	0.0301 (6)	0.0003 (6)	0.0057 (6)	0.0078 (5)
C5	0.0249 (5)	0.0298 (5)	0.0254 (6)	0.0010 (4)	0.0018 (5)	0.0003 (5)
C6	0.0208 (5)	0.0251 (5)	0.0257 (5)	0.0002 (4)	−0.0004 (4)	−0.0004 (4)
C7	0.0291 (5)	0.0253 (6)	0.0292 (6)	0.0010 (4)	0.0021 (5)	0.0003 (4)
C8	0.0287 (6)	0.0335 (6)	0.0285 (6)	0.0018 (4)	0.0013 (5)	−0.0058 (5)
C9	0.0244 (6)	0.0420 (7)	0.0227 (5)	0.0000 (5)	0.0015 (4)	0.0028 (5)
C10	0.0287 (5)	0.0292 (6)	0.0312 (6)	0.0002 (4)	0.0005 (5)	0.0046 (5)
C11	0.0247 (5)	0.0260 (5)	0.0268 (5)	0.0001 (4)	−0.0016 (4)	0.0006 (5)

Geometric parameters (Å, º) top

Cl1—C9	1.7442 (14)	C4—C5	1.4964 (19)
O1—C2	1.3664 (19)	C4—H4A	0.9900
O1—C3	1.455 (2)	C4—H4B	0.9900
N1—C1	1.3332 (19)	C5—C6	1.4074 (19)
N1—C2	1.3420 (19)	C6—C7	1.4178 (16)
N2—C1	1.3599 (19)	C6—C11	1.4244 (17)
N2—H2A	0.82 (3)	C7—C8	1.3725 (19)
N2—H2B	0.80 (3)	C7—H7	0.9500
C1—C11	1.4457 (18)	C8—C9	1.403 (2)
C2—C5	1.3649 (18)	C8—H8	0.9500
C3—C4	1.542 (2)	C9—C10	1.370 (2)
C3—H3A	0.9900	C10—C11	1.4070 (18)
C3—H3B	0.9900	C10—H10	0.9500

C2—O1—C3	106.83 (11)	H4A—C4—H4B	109.3
C1—N1—C2	115.01 (12)	C2—C5—C6	117.37 (12)
C1—N2—H2A	119.8 (17)	C2—C5—C4	109.61 (13)
C1—N2—H2B	119.1 (18)	C6—C5—C4	133.01 (12)
H2A—N2—H2B	117 (2)	C5—C6—C7	123.62 (11)
N1—C1—N2	116.10 (14)	C5—C6—C11	117.81 (11)
N1—C1—C11	123.56 (12)	C7—C6—C11	118.57 (11)
N2—C1—C11	120.31 (14)	C8—C7—C6	121.09 (11)
N1—C2—C5	128.38 (14)	C8—C7—H7	119.5
N1—C2—O1	117.60 (12)	C6—C7—H7	119.5
C5—C2—O1	114.02 (13)	C7—C8—C9	119.00 (12)
O1—C3—C4	108.27 (11)	C7—C8—H8	120.5
O1—C3—H3A	110.0	C9—C8—H8	120.5
C4—C3—H3A	110.0	C10—C9—C8	122.23 (13)
O1—C3—H3B	110.0	C10—C9—Cl1	119.05 (11)
C4—C3—H3B	110.0	C8—C9—Cl1	118.72 (11)
H3A—C3—H3B	108.4	C9—C10—C11	119.39 (12)
C5—C4—C3	101.21 (12)	C9—C10—H10	120.3
C5—C4—H4A	111.5	C11—C10—H10	120.3
C3—C4—H4A	111.5	C10—C11—C6	119.69 (11)
C5—C4—H4B	111.5	C10—C11—C1	122.46 (11)
C3—C4—H4B	111.5	C6—C11—C1	117.84 (12)

C2—N1—C1—N2	179.28 (16)	C5—C6—C7—C8	178.39 (12)
C2—N1—C1—C11	1.50 (19)	C11—C6—C7—C8	−1.19 (18)
C1—N1—C2—C5	−0.1 (2)	C6—C7—C8—C9	0.94 (19)
C1—N1—C2—O1	179.54 (13)	C7—C8—C9—C10	0.0 (2)
C3—O1—C2—N1	179.39 (14)	C7—C8—C9—Cl1	−179.77 (10)
C3—O1—C2—C5	−0.90 (17)	C8—C9—C10—C11	−0.57 (19)
C2—O1—C3—C4	2.07 (17)	Cl1—C9—C10—C11	179.17 (10)
O1—C3—C4—C5	−2.34 (17)	C9—C10—C11—C6	0.29 (18)
N1—C2—C5—C6	−0.5 (2)	C9—C10—C11—C1	179.68 (12)
O1—C2—C5—C6	179.87 (11)	C5—C6—C11—C10	−179.03 (11)
N1—C2—C5—C4	178.97 (15)	C7—C6—C11—C10	0.57 (17)
O1—C2—C5—C4	−0.69 (17)	C5—C6—C11—C1	1.54 (16)
C3—C4—C5—C2	1.84 (16)	C7—C6—C11—C1	−178.85 (11)
C3—C4—C5—C6	−178.84 (13)	N1—C1—C11—C10	178.34 (13)
C2—C5—C6—C7	−179.90 (12)	N2—C1—C11—C10	0.6 (2)
C4—C5—C6—C7	0.8 (2)	N1—C1—C11—C6	−2.26 (18)
C2—C5—C6—C11	−0.32 (17)	N2—C1—C11—C6	−179.95 (15)
C4—C5—C6—C11	−179.60 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O1ⁱ	0.82 (2)	2.43 (2)	3.062 (2)	134 (2)

Symmetry code: (i) −x+1, −y+1, z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₁H₉ClN₂O
M_r	220.66
Crystal system, space group	Orthorhombic, Pna2₁
Temperature (K)	200
a, b, c (Å)	7.2948 (6), 12.0703 (11), 10.8869 (8)
V (Å³)	958.60 (14)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.37
Crystal size (mm)	0.40 × 0.25 × 0.08

Data collection
Diffractometer	Rigaku R-AXIS RAPID II
Absorption correction	Numerical (NUMABS; Higashi, 1999)
T_min, T_max	0.896, 0.971
No. of measured, independent and observed [I > 2σ(I)] reflections	11594, 2776, 2531
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.703

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.031, 0.083, 1.11
No. of reflections	2776
No. of parameters	144
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.42, −0.17
Absolute structure	Flack (1983), 1311 Friedel pairs
Absolute structure parameter	−0.02 (5)

Computer programs: PROCESS-AUTO (Rigaku/MSC, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997), CrystalStructure (Rigaku/MSC, 2004) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O1ⁱ	0.82 (2)	2.43 (2)	3.062 (2)	134 (2)

Symmetry code: (i) −x+1, −y+1, z+1/2.

Acknowledgements

This work was partly supported by a Grant-in-Aid for Scientific Research (C) (No. 22550013) from Japan Society for the Promotion of Science.

References

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