organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

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

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 ππ 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[Okuda, K., Yoshida, M., Hirota, T. & Sasaki, K. (2010). Chem. Pharm. Bull. 58, 363-368.]).

[Scheme 1]

Experimental

Crystal data
  • C11H9ClN2O

  • Mr = 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[Higashi, T. (1999). NUMABS. Rigaku Corporation, Tokyo, Japan.]) Tmin = 0.896, Tmax = 0.971

  • 11594 measured reflections

  • 2776 independent reflections

  • 2531 reflections with I > 2σ(I)

  • Rint = 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

  • Δρmax = 0.42 e Å−3

  • Δρmin = −0.17 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 1311 Friedel pairs

  • Flack parameter: −0.02 (5)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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[Rigaku/MSC (2004). PROCESS-AUTO and CrystalStructure. Rigaku/MSC Inc., The Woodlands, Texas, USA.]); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2004[Rigaku/MSC (2004). PROCESS-AUTO and CrystalStructure. Rigaku/MSC Inc., The Woodlands, Texas, USA.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2004[Rigaku/MSC (2004). PROCESS-AUTO and CrystalStructure. Rigaku/MSC Inc., The Woodlands, Texas, USA.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information


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 ππ 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.

Refinement top

C-bound H atoms were positioned geometrically (C—H = 0.95 or 0.99 Å) and refined as riding, with Uiso(H) = 1.2Ueq(C). The N-bound H atoms were found in a difference Fourier map and refined isotropically. The refined N—H distancea are 0.80 (3) anf 0.82 (3) Å. The Hooft y parameter value is -0.002 (13).

Structure description 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 ππ 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.]

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
[Figure 1] 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.
[Figure 2] 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
C11H9ClN2OF(000) = 456.00
Mr = 220.66Dx = 1.529 Mg m3
Orthorhombic, Pna21Mo Kα radiation, λ = 0.71075 Å
Hall symbol: P 2c -2nCell parameters from 10138 reflections
a = 7.2948 (6) Åθ = 3.3–30.0°
b = 12.0703 (11) ŵ = 0.37 mm1
c = 10.8869 (8) ÅT = 200 K
V = 958.60 (14) Å3Platelet, yellow
Z = 40.40 × 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-1Rint = 0.016
ω scansθmax = 30.0°
Absorption correction: numerical
(NUMABS; Higashi, 1999)
h = 109
Tmin = 0.896, Tmax = 0.971k = 1616
11594 measured reflectionsl = 1515
2776 independent reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.031H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.083 w = 1/[σ2(Fo2) + (0.056P)2 + 0.0168P]
where P = (Fo2 + 2Fc2)/3
S = 1.11(Δ/σ)max = 0.001
2776 reflectionsΔρmax = 0.42 e Å3
144 parametersΔρmin = 0.17 e Å3
1 restraintAbsolute structure: Flack (1983), 1311 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.02 (5)
Crystal data top
C11H9ClN2OV = 958.60 (14) Å3
Mr = 220.66Z = 4
Orthorhombic, Pna21Mo Kα radiation
a = 7.2948 (6) ŵ = 0.37 mm1
b = 12.0703 (11) ÅT = 200 K
c = 10.8869 (8) Å0.40 × 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)
Tmin = 0.896, Tmax = 0.971Rint = 0.016
11594 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.031H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.083Δρmax = 0.42 e Å3
S = 1.11Δρmin = 0.17 e Å3
2776 reflectionsAbsolute structure: Flack (1983), 1311 Friedel pairs
144 parametersAbsolute 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
xyzUiso*/Ueq
Cl10.20651 (5)0.70539 (3)0.83910 (3)0.04205 (11)
O10.5523 (2)0.71804 (10)0.14408 (11)0.0454 (3)
N10.49290 (17)0.58990 (10)0.29743 (12)0.0364 (3)
N20.4320 (3)0.46639 (12)0.4512 (2)0.0522 (4)
C10.44057 (18)0.57365 (11)0.41337 (13)0.0328 (3)
C20.49833 (18)0.69629 (12)0.26182 (13)0.0317 (3)
C30.5446 (2)0.83764 (15)0.12840 (14)0.0431 (3)
H3A0.45510.85690.06350.052*
H3B0.66640.86620.10370.052*
C40.4862 (2)0.88976 (13)0.25161 (14)0.0375 (3)
H4A0.58390.93760.28580.045*
H4B0.37200.93330.24300.045*
C50.45715 (16)0.78864 (9)0.32871 (13)0.0267 (2)
C60.39999 (16)0.77295 (10)0.45094 (12)0.0239 (2)
C70.35257 (17)0.86096 (10)0.53113 (12)0.0279 (2)
H70.36190.93530.50300.033*
C80.29337 (17)0.84059 (12)0.64864 (12)0.0302 (3)
H80.26020.90000.70130.036*
C90.28264 (17)0.73061 (12)0.68982 (13)0.0297 (3)
C100.32916 (18)0.64268 (11)0.61666 (12)0.0297 (3)
H100.32150.56920.64740.036*
C110.38839 (17)0.66225 (10)0.49559 (12)0.0258 (2)
H2A0.430 (3)0.4520 (19)0.525 (2)0.054 (6)*
H2B0.466 (4)0.418 (2)0.406 (2)0.069 (8)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.04108 (18)0.0588 (2)0.02626 (15)0.00458 (13)0.00713 (15)0.00747 (16)
O10.0576 (7)0.0536 (7)0.0249 (5)0.0026 (5)0.0091 (5)0.0055 (4)
N10.0402 (6)0.0329 (6)0.0361 (6)0.0028 (4)0.0018 (5)0.0093 (5)
N20.0730 (10)0.0248 (6)0.0588 (10)0.0045 (6)0.0114 (8)0.0006 (6)
C10.0332 (6)0.0269 (6)0.0382 (7)0.0012 (5)0.0001 (5)0.0036 (5)
C20.0300 (6)0.0396 (7)0.0254 (6)0.0021 (5)0.0013 (5)0.0046 (5)
C30.0492 (8)0.0533 (9)0.0267 (6)0.0020 (7)0.0044 (6)0.0073 (6)
C40.0435 (7)0.0388 (7)0.0301 (6)0.0003 (6)0.0057 (6)0.0078 (5)
C50.0249 (5)0.0298 (5)0.0254 (6)0.0010 (4)0.0018 (5)0.0003 (5)
C60.0208 (5)0.0251 (5)0.0257 (5)0.0002 (4)0.0004 (4)0.0004 (4)
C70.0291 (5)0.0253 (6)0.0292 (6)0.0010 (4)0.0021 (5)0.0003 (4)
C80.0287 (6)0.0335 (6)0.0285 (6)0.0018 (4)0.0013 (5)0.0058 (5)
C90.0244 (6)0.0420 (7)0.0227 (5)0.0000 (5)0.0015 (4)0.0028 (5)
C100.0287 (5)0.0292 (6)0.0312 (6)0.0002 (4)0.0005 (5)0.0046 (5)
C110.0247 (5)0.0260 (5)0.0268 (5)0.0001 (4)0.0016 (4)0.0006 (5)
Geometric parameters (Å, º) top
Cl1—C91.7442 (14)C4—C51.4964 (19)
O1—C21.3664 (19)C4—H4A0.9900
O1—C31.455 (2)C4—H4B0.9900
N1—C11.3332 (19)C5—C61.4074 (19)
N1—C21.3420 (19)C6—C71.4178 (16)
N2—C11.3599 (19)C6—C111.4244 (17)
N2—H2A0.82 (3)C7—C81.3725 (19)
N2—H2B0.80 (3)C7—H70.9500
C1—C111.4457 (18)C8—C91.403 (2)
C2—C51.3649 (18)C8—H80.9500
C3—C41.542 (2)C9—C101.370 (2)
C3—H3A0.9900C10—C111.4070 (18)
C3—H3B0.9900C10—H100.9500
C2—O1—C3106.83 (11)H4A—C4—H4B109.3
C1—N1—C2115.01 (12)C2—C5—C6117.37 (12)
C1—N2—H2A119.8 (17)C2—C5—C4109.61 (13)
C1—N2—H2B119.1 (18)C6—C5—C4133.01 (12)
H2A—N2—H2B117 (2)C5—C6—C7123.62 (11)
N1—C1—N2116.10 (14)C5—C6—C11117.81 (11)
N1—C1—C11123.56 (12)C7—C6—C11118.57 (11)
N2—C1—C11120.31 (14)C8—C7—C6121.09 (11)
N1—C2—C5128.38 (14)C8—C7—H7119.5
N1—C2—O1117.60 (12)C6—C7—H7119.5
C5—C2—O1114.02 (13)C7—C8—C9119.00 (12)
O1—C3—C4108.27 (11)C7—C8—H8120.5
O1—C3—H3A110.0C9—C8—H8120.5
C4—C3—H3A110.0C10—C9—C8122.23 (13)
O1—C3—H3B110.0C10—C9—Cl1119.05 (11)
C4—C3—H3B110.0C8—C9—Cl1118.72 (11)
H3A—C3—H3B108.4C9—C10—C11119.39 (12)
C5—C4—C3101.21 (12)C9—C10—H10120.3
C5—C4—H4A111.5C11—C10—H10120.3
C3—C4—H4A111.5C10—C11—C6119.69 (11)
C5—C4—H4B111.5C10—C11—C1122.46 (11)
C3—C4—H4B111.5C6—C11—C1117.84 (12)
C2—N1—C1—N2179.28 (16)C5—C6—C7—C8178.39 (12)
C2—N1—C1—C111.50 (19)C11—C6—C7—C81.19 (18)
C1—N1—C2—C50.1 (2)C6—C7—C8—C90.94 (19)
C1—N1—C2—O1179.54 (13)C7—C8—C9—C100.0 (2)
C3—O1—C2—N1179.39 (14)C7—C8—C9—Cl1179.77 (10)
C3—O1—C2—C50.90 (17)C8—C9—C10—C110.57 (19)
C2—O1—C3—C42.07 (17)Cl1—C9—C10—C11179.17 (10)
O1—C3—C4—C52.34 (17)C9—C10—C11—C60.29 (18)
N1—C2—C5—C60.5 (2)C9—C10—C11—C1179.68 (12)
O1—C2—C5—C6179.87 (11)C5—C6—C11—C10179.03 (11)
N1—C2—C5—C4178.97 (15)C7—C6—C11—C100.57 (17)
O1—C2—C5—C40.69 (17)C5—C6—C11—C11.54 (16)
C3—C4—C5—C21.84 (16)C7—C6—C11—C1178.85 (11)
C3—C4—C5—C6178.84 (13)N1—C1—C11—C10178.34 (13)
C2—C5—C6—C7179.90 (12)N2—C1—C11—C100.6 (2)
C4—C5—C6—C70.8 (2)N1—C1—C11—C62.26 (18)
C2—C5—C6—C110.32 (17)N2—C1—C11—C6179.95 (15)
C4—C5—C6—C11179.60 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···O1i0.82 (2)2.43 (2)3.062 (2)134 (2)
Symmetry code: (i) x+1, y+1, z+1/2.

Experimental details

Crystal data
Chemical formulaC11H9ClN2O
Mr220.66
Crystal system, space groupOrthorhombic, Pna21
Temperature (K)200
a, b, c (Å)7.2948 (6), 12.0703 (11), 10.8869 (8)
V3)958.60 (14)
Z4
Radiation typeMo Kα
µ (mm1)0.37
Crystal size (mm)0.40 × 0.25 × 0.08
Data collection
DiffractometerRigaku R-AXIS RAPID II
Absorption correctionNumerical
(NUMABS; Higashi, 1999)
Tmin, Tmax0.896, 0.971
No. of measured, independent and
observed [I > 2σ(I)] reflections
11594, 2776, 2531
Rint0.016
(sin θ/λ)max1)0.703
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.031, 0.083, 1.11
No. of reflections2776
No. of parameters144
No. of restraints1
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.42, 0.17
Absolute structureFlack (1983), 1311 Friedel pairs
Absolute structure parameter0.02 (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···AD—HH···AD···AD—H···A
N2—H2A···O1i0.82 (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

First citationFarrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  CrossRef IUCr Journals Google Scholar
First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationHigashi, T. (1999). NUMABS. Rigaku Corporation, Tokyo, Japan.  Google Scholar
First citationOkuda, K., Yoshida, M., Hirota, T. & Sasaki, K. (2010). Chem. Pharm. Bull. 58, 363–368.  CrossRef CAS PubMed Google Scholar
First citationRigaku/MSC (2004). PROCESS-AUTO and CrystalStructure. Rigaku/MSC Inc., The Woodlands, Texas, USA.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds