(1S*,4'S*,5R*)-1-Isobutyl-5-meth-oxy-2',3-dimethyl-4,6-dioxa-2-aza-spiro-[bicyclo-[3.2.0]hept-2-ene-7,4'-isoquinoline]-1',3'(2'H,4'H)-dione.

In the isoquinoline ring system of the title compound, C(19)H(22)N(2)O(5), the N-heterocyclic ring is in a half-chair conformation. The dioxa-2-aza-spiro ring is essentially planar [maximum deviation of 0.025 (1) Å] and forms a dihedral angle of 23.51 (5)° with the benzene ring. In the crystal, mol-ecules are linked via weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds into chains along [010].

Related literature

For general background to and the potential biological activity of the title compound, see: Pollers-Wieers et al. (1981 ▶); Malamas et al. (1994 ▶); Yu et al. (2010 ▶); Du et al. (2008 ▶); Chen et al. (2006 ▶); Zhang et al. (2006 ▶); Mitchell et al. (1995 ▶, 2000 ▶); Harris et al. (2005 ▶); Wang et al. (2010 ▶); Huang et al. (2011 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶). For standard bond-length data, see: Allen et al. (1987 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For a related structure, see: Fun et al. (2011 ▶).

Experimental

Crystal data

C19H22N2O5

M = 358.39

Monoclinic,

a = 8.0488 (1) Å

b = 13.6065 (2) Å

c = 16.7880 (2) Å

β = 106.298 (1)°

V = 1764.67 (4) Å3

Z = 4

Mo Kα radiation

μ = 0.10 mm−1

T = 100 K

0.25 × 0.16 × 0.12 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T min = 0.976, T max = 0.988

24267 measured reflections

5139 independent reflections

4476 reflections with I > 2σ(I)

R int = 0.025

Refinement

R[F 2 > 2σ(F 2)] = 0.038

wR(F 2) = 0.103

S = 1.03

5139 reflections

240 parameters

H-atom parameters constrained

Δρmax = 0.44 e Å−3

Δρmin = −0.24 e Å−3

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811015327/lh5238sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811015327/lh5238Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C19H22N2O5	F(000) = 760
Mr = 358.39	Dx = 1.349 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 9893 reflections
a = 8.0488 (1) Å	θ = 3.0–35.8°
b = 13.6065 (2) Å	µ = 0.10 mm−1
c = 16.7880 (2) Å	T = 100 K
β = 106.298 (1)°	Block, colourless
V = 1764.67 (4) Å3	0.25 × 0.16 × 0.12 mm
Z = 4

Bruker SMART APEXII CCD area-detector diffractometer	5139 independent reflections
Radiation source: fine-focus sealed tube	4476 reflections with I > 2σ(I)
graphite	Rint = 0.025
φ and ω scans	θmax = 30.0°, θmin = 2.5°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −11→11
Tmin = 0.976, Tmax = 0.988	k = −19→19
24267 measured reflections	l = −23→23

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.103	H-atom parameters constrained
S = 1.03	w = 1/[σ2(Fo2) + (0.0553P)2 + 0.5274P] where P = (Fo2 + 2Fc2)/3
5139 reflections	(Δ/σ)max = 0.001
240 parameters	Δρmax = 0.44 e Å−3
0 restraints	Δρmin = −0.24 e Å−3

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.

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.

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 > 2sigma(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.

	x	y	z	Uiso*/Ueq
O1	0.79496 (9)	0.57309 (5)	0.66503 (5)	0.02050 (15)
O2	1.34091 (9)	0.52679 (5)	0.64902 (5)	0.02368 (16)
O3	0.82385 (8)	0.77489 (5)	0.67549 (4)	0.01707 (14)
O4	0.57984 (8)	0.76986 (5)	0.55910 (4)	0.01918 (15)
O5	0.74064 (9)	0.91191 (5)	0.58917 (5)	0.02068 (15)
N1	1.05809 (10)	0.55116 (6)	0.64124 (5)	0.01658 (16)
N2	0.75988 (10)	0.67859 (6)	0.50490 (5)	0.01618 (16)
C1	0.92559 (11)	0.60875 (7)	0.65547 (5)	0.01528 (17)
C2	1.22975 (11)	0.58267 (7)	0.65818 (6)	0.01617 (17)
C3	1.26757 (11)	0.68377 (7)	0.69139 (6)	0.01539 (17)
C4	1.44041 (12)	0.71107 (7)	0.72596 (6)	0.01982 (19)
H4A	1.5292	0.6675	0.7255	0.024*
C5	1.47831 (12)	0.80359 (8)	0.76086 (6)	0.0219 (2)
H5A	1.5927	0.8212	0.7859	0.026*
C6	1.34573 (13)	0.87042 (7)	0.75865 (6)	0.01974 (19)
H6A	1.3722	0.9327	0.7815	0.024*
C7	1.17372 (12)	0.84428 (7)	0.72237 (6)	0.01706 (17)
H7A	1.0857	0.8895	0.7198	0.020*
C8	1.13408 (11)	0.75022 (7)	0.68989 (5)	0.01429 (16)
C9	0.95168 (11)	0.71880 (6)	0.64877 (5)	0.01391 (16)
C10	0.74669 (11)	0.81247 (7)	0.59376 (6)	0.01633 (17)
C11	0.60784 (12)	0.69179 (7)	0.51199 (6)	0.01745 (18)
C12	0.86979 (11)	0.75430 (7)	0.55523 (5)	0.01432 (16)
C13	0.99210 (11)	0.80256 (7)	0.51287 (6)	0.01624 (17)
H13A	1.0911	0.7597	0.5187	0.019*
H13B	1.0343	0.8632	0.5419	0.019*
C14	0.91552 (13)	0.82618 (7)	0.42050 (6)	0.01925 (18)
H14A	0.8691	0.7654	0.3914	0.023*
C15	0.76970 (14)	0.90189 (8)	0.40468 (7)	0.0259 (2)
H15A	0.6740	0.8751	0.4211	0.039*
H15B	0.7328	0.9179	0.3467	0.039*
H15C	0.8106	0.9602	0.4363	0.039*
C16	1.06068 (15)	0.86338 (9)	0.38598 (7)	0.0274 (2)
H16A	1.1485	0.8138	0.3932	0.041*
H16B	1.1101	0.9219	0.4151	0.041*
H16C	1.0146	0.8778	0.3280	0.041*
C17	1.02112 (14)	0.44773 (7)	0.61770 (7)	0.0245 (2)
H17A	0.9002	0.4403	0.5898	0.037*
H17B	1.0509	0.4075	0.6666	0.037*
H17C	1.0881	0.4279	0.5813	0.037*
C18	0.62742 (16)	0.95764 (8)	0.63135 (9)	0.0323 (3)
H18A	0.6249	1.0273	0.6220	0.048*
H18B	0.6693	0.9447	0.6898	0.048*
H18C	0.5127	0.9314	0.6103	0.048*
C19	0.45239 (12)	0.63113 (8)	0.47491 (7)	0.0226 (2)
H19A	0.4805	0.5812	0.4404	0.034*
H19B	0.3618	0.6721	0.4421	0.034*
H19C	0.4143	0.6007	0.5183	0.034*

	U11	U22	U33	U12	U13	U23
O1	0.0177 (3)	0.0217 (3)	0.0236 (3)	−0.0037 (3)	0.0082 (3)	0.0008 (3)
O2	0.0187 (3)	0.0198 (3)	0.0330 (4)	0.0042 (3)	0.0081 (3)	−0.0012 (3)
O3	0.0149 (3)	0.0201 (3)	0.0172 (3)	0.0031 (2)	0.0062 (2)	−0.0021 (2)
O4	0.0126 (3)	0.0210 (3)	0.0236 (4)	0.0003 (2)	0.0045 (2)	−0.0023 (3)
O5	0.0209 (3)	0.0146 (3)	0.0297 (4)	0.0029 (2)	0.0123 (3)	−0.0011 (3)
N1	0.0156 (3)	0.0137 (3)	0.0207 (4)	−0.0006 (3)	0.0056 (3)	−0.0008 (3)
N2	0.0156 (3)	0.0163 (4)	0.0151 (4)	−0.0011 (3)	0.0018 (3)	−0.0005 (3)
C1	0.0155 (4)	0.0165 (4)	0.0135 (4)	−0.0004 (3)	0.0034 (3)	0.0001 (3)
C2	0.0151 (4)	0.0166 (4)	0.0164 (4)	0.0010 (3)	0.0039 (3)	0.0021 (3)
C3	0.0144 (4)	0.0166 (4)	0.0149 (4)	0.0001 (3)	0.0036 (3)	0.0008 (3)
C4	0.0145 (4)	0.0223 (5)	0.0213 (4)	0.0010 (3)	0.0027 (3)	0.0022 (4)
C5	0.0163 (4)	0.0247 (5)	0.0218 (5)	−0.0041 (3)	0.0005 (3)	0.0009 (4)
C6	0.0220 (4)	0.0196 (4)	0.0166 (4)	−0.0048 (3)	0.0037 (3)	−0.0022 (3)
C7	0.0180 (4)	0.0176 (4)	0.0159 (4)	−0.0002 (3)	0.0054 (3)	−0.0013 (3)
C8	0.0138 (4)	0.0167 (4)	0.0125 (4)	−0.0005 (3)	0.0038 (3)	0.0006 (3)
C9	0.0127 (4)	0.0152 (4)	0.0147 (4)	0.0008 (3)	0.0053 (3)	−0.0012 (3)
C10	0.0135 (4)	0.0163 (4)	0.0193 (4)	0.0009 (3)	0.0050 (3)	−0.0006 (3)
C11	0.0166 (4)	0.0175 (4)	0.0167 (4)	−0.0001 (3)	0.0023 (3)	0.0015 (3)
C12	0.0133 (4)	0.0147 (4)	0.0145 (4)	0.0015 (3)	0.0033 (3)	−0.0005 (3)
C13	0.0156 (4)	0.0177 (4)	0.0157 (4)	−0.0001 (3)	0.0048 (3)	0.0008 (3)
C14	0.0237 (4)	0.0172 (4)	0.0160 (4)	−0.0003 (3)	0.0041 (3)	0.0003 (3)
C15	0.0270 (5)	0.0243 (5)	0.0229 (5)	0.0044 (4)	0.0011 (4)	0.0045 (4)
C16	0.0345 (6)	0.0300 (6)	0.0210 (5)	0.0003 (4)	0.0133 (4)	0.0043 (4)
C17	0.0248 (5)	0.0156 (4)	0.0353 (6)	−0.0031 (4)	0.0122 (4)	−0.0051 (4)
C18	0.0340 (6)	0.0195 (5)	0.0530 (8)	0.0043 (4)	0.0281 (5)	−0.0040 (5)
C19	0.0174 (4)	0.0243 (5)	0.0235 (5)	−0.0044 (3)	0.0015 (3)	0.0008 (4)

O1—C1	1.2088 (11)	C9—C12	1.5978 (12)
O2—C2	1.2164 (11)	C10—C12	1.5447 (12)
O3—C10	1.4323 (11)	C11—C19	1.4823 (13)
O3—C9	1.4496 (10)	C12—C13	1.5162 (12)
O4—C11	1.3801 (12)	C13—C14	1.5334 (13)
O4—C10	1.4282 (11)	C13—H13A	0.9700
O5—C10	1.3554 (11)	C13—H13B	0.9700
O5—C18	1.4428 (12)	C14—C15	1.5278 (14)
N1—C1	1.3970 (11)	C14—C16	1.5288 (14)
N1—C2	1.3976 (11)	C14—H14A	0.9800
N1—C17	1.4694 (12)	C15—H15A	0.9600
N2—C11	1.2750 (12)	C15—H15B	0.9600
N2—C12	1.4623 (12)	C15—H15C	0.9600
C1—C9	1.5205 (13)	C16—H16A	0.9600
C2—C3	1.4834 (13)	C16—H16B	0.9600
C3—C4	1.3989 (12)	C16—H16C	0.9600
C3—C8	1.3990 (12)	C17—H17A	0.9600
C4—C5	1.3860 (14)	C17—H17B	0.9600
C4—H4A	0.9300	C17—H17C	0.9600
C5—C6	1.3945 (14)	C18—H18A	0.9600
C5—H5A	0.9300	C18—H18B	0.9600
C6—C7	1.3932 (13)	C18—H18C	0.9600
C6—H6A	0.9300	C19—H19A	0.9600
C7—C8	1.3926 (13)	C19—H19B	0.9600
C7—H7A	0.9300	C19—H19C	0.9600
C8—C9	1.4987 (12)
C10—O3—C9	92.64 (6)	N2—C12—C10	104.34 (7)
C11—O4—C10	105.06 (7)	C13—C12—C10	123.48 (8)
C10—O5—C18	114.85 (8)	N2—C12—C9	111.75 (7)
C1—N1—C2	123.48 (8)	C13—C12—C9	116.67 (7)
C1—N1—C17	118.46 (8)	C10—C12—C9	83.08 (6)
C2—N1—C17	117.55 (8)	C12—C13—C14	115.81 (8)
C11—N2—C12	106.72 (8)	C12—C13—H13A	108.3
O1—C1—N1	122.12 (9)	C14—C13—H13A	108.3
O1—C1—C9	123.26 (8)	C12—C13—H13B	108.3
N1—C1—C9	114.32 (7)	C14—C13—H13B	108.3
O2—C2—N1	120.18 (9)	H13A—C13—H13B	107.4
O2—C2—C3	123.13 (8)	C15—C14—C16	110.02 (9)
N1—C2—C3	116.61 (8)	C15—C14—C13	112.85 (8)
C4—C3—C8	120.34 (9)	C16—C14—C13	108.64 (8)
C4—C3—C2	118.52 (8)	C15—C14—H14A	108.4
C8—C3—C2	121.13 (8)	C16—C14—H14A	108.4
C5—C4—C3	119.46 (9)	C13—C14—H14A	108.4
C5—C4—H4A	120.3	C14—C15—H15A	109.5
C3—C4—H4A	120.3	C14—C15—H15B	109.5
C4—C5—C6	120.33 (9)	H15A—C15—H15B	109.5
C4—C5—H5A	119.8	C14—C15—H15C	109.5
C6—C5—H5A	119.8	H15A—C15—H15C	109.5
C7—C6—C5	120.29 (9)	H15B—C15—H15C	109.5
C7—C6—H6A	119.9	C14—C16—H16A	109.5
C5—C6—H6A	119.9	C14—C16—H16B	109.5
C8—C7—C6	119.74 (9)	H16A—C16—H16B	109.5
C8—C7—H7A	120.1	C14—C16—H16C	109.5
C6—C7—H7A	120.1	H16A—C16—H16C	109.5
C7—C8—C3	119.77 (8)	H16B—C16—H16C	109.5
C7—C8—C9	121.99 (8)	N1—C17—H17A	109.5
C3—C8—C9	118.17 (8)	N1—C17—H17B	109.5
O3—C9—C8	113.32 (7)	H17A—C17—H17B	109.5
O3—C9—C1	111.77 (7)	N1—C17—H17C	109.5
C8—C9—C1	112.62 (7)	H17A—C17—H17C	109.5
O3—C9—C12	90.69 (6)	H17B—C17—H17C	109.5
C8—C9—C12	116.56 (7)	O5—C18—H18A	109.5
C1—C9—C12	110.06 (7)	O5—C18—H18B	109.5
O5—C10—O4	111.56 (7)	H18A—C18—H18B	109.5
O5—C10—O3	114.19 (8)	O5—C18—H18C	109.5
O4—C10—O3	110.53 (7)	H18A—C18—H18C	109.5
O5—C10—C12	120.31 (8)	H18B—C18—H18C	109.5
O4—C10—C12	105.17 (7)	C11—C19—H19A	109.5
O3—C10—C12	93.54 (6)	C11—C19—H19B	109.5
N2—C11—O4	118.51 (8)	H19A—C19—H19B	109.5
N2—C11—C19	126.98 (9)	C11—C19—H19C	109.5
O4—C11—C19	114.51 (8)	H19A—C19—H19C	109.5
N2—C12—C13	113.66 (7)	H19B—C19—H19C	109.5
C2—N1—C1—O1	−156.91 (9)	C18—O5—C10—O3	−66.90 (11)
C17—N1—C1—O1	14.72 (14)	C18—O5—C10—C12	−176.84 (9)
C2—N1—C1—C9	29.21 (12)	C11—O4—C10—O5	136.31 (8)
C17—N1—C1—C9	−159.16 (8)	C11—O4—C10—O3	−95.49 (8)
C1—N1—C2—O2	175.59 (9)	C11—O4—C10—C12	4.29 (9)
C17—N1—C2—O2	3.89 (13)	C9—O3—C10—O5	−123.77 (8)
C1—N1—C2—C3	−1.26 (13)	C9—O3—C10—O4	109.48 (7)
C17—N1—C2—C3	−172.97 (8)	C9—O3—C10—C12	1.83 (7)
O2—C2—C3—C4	−10.44 (14)	C12—N2—C11—O4	2.05 (11)
N1—C2—C3—C4	166.32 (8)	C12—N2—C11—C19	−177.58 (9)
O2—C2—C3—C8	170.78 (9)	C10—O4—C11—N2	−4.29 (11)
N1—C2—C3—C8	−12.46 (13)	C10—O4—C11—C19	175.38 (8)
C8—C3—C4—C5	1.80 (14)	C11—N2—C12—C13	−136.26 (8)
C2—C3—C4—C5	−176.99 (9)	C11—N2—C12—C10	0.94 (10)
C3—C4—C5—C6	−2.53 (15)	C11—N2—C12—C9	89.12 (9)
C4—C5—C6—C7	0.91 (15)	O5—C10—C12—N2	−130.14 (9)
C5—C6—C7—C8	1.46 (14)	O4—C10—C12—N2	−3.31 (9)
C6—C7—C8—C3	−2.17 (13)	O3—C10—C12—N2	109.08 (7)
C6—C7—C8—C9	−178.83 (8)	O5—C10—C12—C13	1.60 (13)
C4—C3—C8—C7	0.55 (14)	O4—C10—C12—C13	128.44 (8)
C2—C3—C8—C7	179.30 (8)	O3—C10—C12—C13	−119.18 (8)
C4—C3—C8—C9	177.34 (8)	O5—C10—C12—C9	119.11 (9)
C2—C3—C8—C9	−3.91 (13)	O4—C10—C12—C9	−114.06 (7)
C10—O3—C9—C8	117.71 (8)	O3—C10—C12—C9	−1.67 (6)
C10—O3—C9—C1	−113.75 (8)	O3—C9—C12—N2	−101.08 (7)
C10—O3—C9—C12	−1.77 (6)	C8—C9—C12—N2	142.27 (8)
C7—C8—C9—O3	−24.24 (12)	C1—C9—C12—N2	12.45 (9)
C3—C8—C9—O3	159.04 (8)	O3—C9—C12—C13	125.77 (8)
C7—C8—C9—C1	−152.34 (8)	C8—C9—C12—C13	9.11 (11)
C3—C8—C9—C1	30.94 (11)	C1—C9—C12—C13	−120.70 (8)
C7—C8—C9—C12	79.06 (10)	O3—C9—C12—C10	1.65 (6)
C3—C8—C9—C12	−97.65 (10)	C8—C9—C12—C10	−115.00 (8)
O1—C1—C9—O3	14.35 (12)	C1—C9—C12—C10	115.18 (7)
N1—C1—C9—O3	−171.86 (7)	N2—C12—C13—C14	41.49 (11)
O1—C1—C9—C8	143.26 (9)	C10—C12—C13—C14	−86.40 (11)
N1—C1—C9—C8	−42.95 (10)	C9—C12—C13—C14	173.78 (7)
O1—C1—C9—C12	−84.84 (10)	C12—C13—C14—C15	64.00 (11)
N1—C1—C9—C12	88.95 (9)	C12—C13—C14—C16	−173.71 (8)
C18—O5—C10—O4	59.32 (11)

D—H···A	D—H	H···A	D···A	D—H···A
C16—H16B···O5i	0.96	2.57	3.4213 (14)	148
C17—H17C···N2ii	0.96	2.59	3.5119 (14)	162

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C16—H16B⋯O5i	0.96	2.57	3.4213 (14)	148
C17—H17C⋯N2ii	0.96	2.59	3.5119 (14)	162

Symmetry codes: (i) ; (ii) .