Methyl 4'-benzyl-2,2'-dimethyl-1,3-dioxo-2,3-dihydro-1H,4'H-spiro-[iso-quinoline-4,5'-oxazole]-4'-carboxyl-ate.

In the isoquinoline ring system of the title mol-ecule, C(22)H(20)N(2)O(5), the N-heterocyclic ring is in a half-boat conformation. The least-squares plane of the dioxa-2-aza-spiro ring [maximum deviation = 0.076 (1) Å] and forms a dihedral angle of 14.54 (4)° with the phenyl ring. In the crystal, mol-ecules are linked via inter-molecular C-H⋯O hydrogen bonds into layers parallel to (100).

Related literature

For general background to and the potential biological activity of the title compound, see: Du et al. (2008 ▶); Chen et al. (2006 ▶); Mitchell et al. (1995 ▶, 2000 ▶); Galliford & Scheidt (2007 ▶); Badillo et al. (2010 ▶); Wang et al. (2010 ▶); Nair et al. (2002 ▶); 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 related structures, see: Fun et al. (2011a ▶,b ▶,c ▶,d ▶).

Experimental

Crystal data

C22H20N2O5

M = 392.40

Triclinic,

a = 8.6834 (7) Å

b = 11.1683 (9) Å

c = 11.3085 (9) Å

α = 100.638 (2)°

β = 106.347 (2)°

γ = 109.383 (2)°

V = 944.72 (13) Å3

Z = 2

Mo Kα radiation

μ = 0.10 mm−1

T = 100 K

0.57 × 0.32 × 0.24 mm

Data collection

Bruker SMART APEXII DUO CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T min = 0.937, T max = 0.977

32434 measured reflections

8179 independent reflections

7354 reflections with I > 2σ(I)

R int = 0.021

Refinement

R[F 2 > 2σ(F 2)] = 0.037

wR(F 2) = 0.109

S = 1.04

8179 reflections

265 parameters

H-atom parameters constrained

Δρmax = 0.52 e Å−3

Δρmin = −0.28 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/S160053681101899X/rz2598sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053681101899X/rz2598Isup2.hkl

Supplementary material file. DOI: 10.1107/S160053681101899X/rz2598Isup3.cml

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

C22H20N2O5	Z = 2
Mr = 392.40	F(000) = 412
Triclinic, P1	Dx = 1.379 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.6834 (7) Å	Cell parameters from 9462 reflections
b = 11.1683 (9) Å	θ = 2.4–37.5°
c = 11.3085 (9) Å	µ = 0.10 mm−1
α = 100.638 (2)°	T = 100 K
β = 106.347 (2)°	Block, colourless
γ = 109.383 (2)°	0.57 × 0.32 × 0.24 mm
V = 944.72 (13) Å3

Bruker SMART APEXII DUO CCD area-detector diffractometer	8179 independent reflections
Radiation source: fine-focus sealed tube	7354 reflections with I > 2σ(I)
graphite	Rint = 0.021
φ and ω scans	θmax = 35.0°, θmin = 2.4°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −14→14
Tmin = 0.937, Tmax = 0.977	k = −15→17
32434 measured reflections	l = −18→18

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)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.109	H-atom parameters constrained
S = 1.04	w = 1/[σ2(Fo2) + (0.0618P)2 + 0.1885P] where P = (Fo2 + 2Fc2)/3
8179 reflections	(Δ/σ)max = 0.001
265 parameters	Δρmax = 0.52 e Å−3
0 restraints	Δρmin = −0.28 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	0.42744 (6)	0.99506 (5)	0.62495 (5)	0.01754 (9)
O2	1.02131 (7)	1.14156 (6)	0.79359 (6)	0.02414 (11)
O3	0.38562 (6)	0.75687 (5)	0.48448 (4)	0.01382 (8)
O4	0.79722 (6)	0.82611 (5)	0.84267 (5)	0.01722 (9)
O5	0.66059 (8)	0.60673 (6)	0.73207 (5)	0.02126 (10)
N1	0.72403 (7)	1.06714 (5)	0.71929 (5)	0.01359 (9)
N2	0.34962 (7)	0.62897 (5)	0.61741 (5)	0.01486 (9)
C1	0.55724 (8)	0.97088 (6)	0.64348 (6)	0.01269 (10)
C2	0.87944 (8)	1.05358 (6)	0.72190 (6)	0.01481 (10)
C3	0.86167 (8)	0.93183 (6)	0.63044 (6)	0.01287 (10)
C4	1.01135 (8)	0.92673 (7)	0.61052 (6)	0.01605 (11)
H4A	1.1205	0.9972	0.6568	0.019*
C5	0.99607 (9)	0.81563 (7)	0.52111 (7)	0.01776 (11)
H5A	1.0950	0.8117	0.5070	0.021*
C6	0.83222 (9)	0.71001 (7)	0.45264 (7)	0.01777 (11)
H6A	0.8221	0.6365	0.3918	0.021*
C7	0.68345 (8)	0.71352 (6)	0.47458 (6)	0.01523 (10)
H7A	0.5750	0.6419	0.4299	0.018*
C8	0.69821 (7)	0.82499 (6)	0.56378 (5)	0.01185 (9)
C9	0.54340 (7)	0.82960 (6)	0.59671 (5)	0.01139 (9)
C10	0.50493 (7)	0.75045 (6)	0.69900 (5)	0.01179 (9)
C11	0.46381 (8)	0.82409 (6)	0.80912 (6)	0.01338 (10)
H11A	0.5604	0.9106	0.8561	0.016*
H11B	0.3589	0.8385	0.7715	0.016*
C12	0.43613 (8)	0.74497 (6)	0.90251 (6)	0.01339 (10)
C13	0.27481 (9)	0.64000 (7)	0.87237 (7)	0.02070 (13)
H13A	0.1812	0.6222	0.7971	0.025*
C14	0.25276 (12)	0.56155 (8)	0.95414 (8)	0.02710 (16)
H14A	0.1448	0.4916	0.9328	0.033*
C15	0.39115 (13)	0.58721 (8)	1.06747 (8)	0.02569 (15)
H15A	0.3768	0.5337	1.1210	0.031*
C16	0.55074 (11)	0.69343 (9)	1.09983 (7)	0.02314 (14)
H16A	0.6432	0.7124	1.1762	0.028*
C17	0.57309 (9)	0.77188 (7)	1.01826 (6)	0.01805 (11)
H17A	0.6805	0.8431	1.0411	0.022*
C18	0.29331 (8)	0.64261 (6)	0.50621 (6)	0.01369 (10)
C19	0.13538 (8)	0.54771 (7)	0.39220 (6)	0.01767 (11)
H19A	0.0703	0.4749	0.4165	0.027*
H19B	0.1709	0.5142	0.3247	0.027*
H19C	0.0627	0.5927	0.3616	0.027*
C20	0.65977 (8)	0.71589 (6)	0.75831 (6)	0.01428 (10)
C21	0.95690 (10)	0.80855 (10)	0.89813 (8)	0.02757 (16)
H21A	1.0476	0.8923	0.9566	0.041*
H21B	0.9932	0.7771	0.8302	0.041*
H21C	0.9360	0.7446	0.9443	0.041*
C22	0.73534 (9)	1.19379 (7)	0.79492 (6)	0.01796 (11)
H22A	0.6594	1.2240	0.7407	0.027*
H22B	0.8542	1.2593	0.8272	0.027*
H22C	0.6998	1.1809	0.8663	0.027*

	U11	U22	U33	U12	U13	U23
O1	0.01526 (19)	0.0181 (2)	0.0226 (2)	0.00961 (17)	0.00716 (17)	0.00806 (17)
O2	0.0138 (2)	0.0238 (3)	0.0220 (2)	0.00140 (18)	0.00273 (17)	−0.00360 (19)
O3	0.01078 (17)	0.01457 (19)	0.01226 (17)	0.00306 (14)	0.00146 (14)	0.00387 (14)
O4	0.01345 (19)	0.0230 (2)	0.01511 (19)	0.00824 (17)	0.00345 (15)	0.00683 (17)
O5	0.0283 (3)	0.0210 (2)	0.0243 (2)	0.0163 (2)	0.0132 (2)	0.01167 (19)
N1	0.0134 (2)	0.0122 (2)	0.0139 (2)	0.00491 (16)	0.00435 (16)	0.00305 (16)
N2	0.0148 (2)	0.0125 (2)	0.0140 (2)	0.00247 (17)	0.00536 (17)	0.00256 (16)
C1	0.0130 (2)	0.0130 (2)	0.0130 (2)	0.00544 (18)	0.00502 (18)	0.00536 (18)
C2	0.0130 (2)	0.0161 (2)	0.0131 (2)	0.00428 (19)	0.00430 (18)	0.00351 (19)
C3	0.0115 (2)	0.0142 (2)	0.0129 (2)	0.00490 (18)	0.00465 (17)	0.00471 (18)
C4	0.0124 (2)	0.0181 (3)	0.0190 (3)	0.0061 (2)	0.00679 (19)	0.0073 (2)
C5	0.0166 (2)	0.0195 (3)	0.0229 (3)	0.0097 (2)	0.0110 (2)	0.0091 (2)
C6	0.0194 (3)	0.0168 (3)	0.0215 (3)	0.0092 (2)	0.0113 (2)	0.0063 (2)
C7	0.0154 (2)	0.0143 (2)	0.0167 (2)	0.00607 (19)	0.00724 (19)	0.00404 (19)
C8	0.0115 (2)	0.0131 (2)	0.0121 (2)	0.00527 (18)	0.00493 (17)	0.00502 (17)
C9	0.0099 (2)	0.0121 (2)	0.0110 (2)	0.00388 (17)	0.00275 (16)	0.00363 (17)
C10	0.0120 (2)	0.0119 (2)	0.0116 (2)	0.00449 (17)	0.00453 (17)	0.00413 (17)
C11	0.0149 (2)	0.0137 (2)	0.0129 (2)	0.00626 (19)	0.00623 (18)	0.00452 (18)
C12	0.0143 (2)	0.0141 (2)	0.0123 (2)	0.00542 (19)	0.00596 (18)	0.00399 (18)
C13	0.0189 (3)	0.0198 (3)	0.0159 (3)	0.0000 (2)	0.0070 (2)	0.0030 (2)
C14	0.0346 (4)	0.0170 (3)	0.0238 (3)	0.0000 (3)	0.0162 (3)	0.0046 (2)
C15	0.0435 (4)	0.0207 (3)	0.0256 (3)	0.0168 (3)	0.0223 (3)	0.0135 (3)
C16	0.0285 (3)	0.0333 (4)	0.0191 (3)	0.0195 (3)	0.0126 (3)	0.0145 (3)
C17	0.0164 (2)	0.0244 (3)	0.0145 (2)	0.0084 (2)	0.0062 (2)	0.0075 (2)
C18	0.0115 (2)	0.0130 (2)	0.0147 (2)	0.00366 (18)	0.00504 (18)	0.00219 (18)
C19	0.0126 (2)	0.0172 (3)	0.0165 (2)	0.0031 (2)	0.00291 (19)	−0.0004 (2)
C20	0.0162 (2)	0.0179 (3)	0.0131 (2)	0.0089 (2)	0.00716 (19)	0.00792 (19)
C21	0.0180 (3)	0.0424 (5)	0.0250 (3)	0.0168 (3)	0.0040 (2)	0.0140 (3)
C22	0.0221 (3)	0.0137 (2)	0.0161 (2)	0.0076 (2)	0.0056 (2)	0.0022 (2)

O1—C1	1.2153 (7)	C10—C20	1.5294 (8)
O2—C2	1.2168 (8)	C10—C11	1.5562 (8)
O3—C18	1.3707 (8)	C11—C12	1.5167 (9)
O3—C9	1.4316 (7)	C11—H11A	0.9700
O4—C20	1.3417 (8)	C11—H11B	0.9700
O4—C21	1.4459 (9)	C12—C13	1.3952 (9)
O5—C20	1.2033 (8)	C12—C17	1.3998 (9)
N1—C1	1.3841 (8)	C13—C14	1.3954 (11)
N1—C2	1.3999 (8)	C13—H13A	0.9300
N1—C22	1.4682 (8)	C14—C15	1.3920 (13)
N2—C18	1.2719 (8)	C14—H14A	0.9300
N2—C10	1.4607 (8)	C15—C16	1.3873 (12)
C1—C9	1.5212 (8)	C15—H15A	0.9300
C2—C3	1.4813 (9)	C16—C17	1.3937 (10)
C3—C8	1.3958 (8)	C16—H16A	0.9300
C3—C4	1.3972 (9)	C17—H17A	0.9300
C4—C5	1.3899 (10)	C18—C19	1.4839 (9)
C4—H4A	0.9300	C19—H19A	0.9600
C5—C6	1.3943 (10)	C19—H19B	0.9600
C5—H5A	0.9300	C19—H19C	0.9600
C6—C7	1.3936 (9)	C21—H21A	0.9600
C6—H6A	0.9300	C21—H21B	0.9600
C7—C8	1.3934 (9)	C21—H21C	0.9600
C7—H7A	0.9300	C22—H22A	0.9600
C8—C9	1.5064 (8)	C22—H22B	0.9600
C9—C10	1.6217 (8)	C22—H22C	0.9600
C18—O3—C9	106.97 (5)	C12—C11—H11B	109.3
C20—O4—C21	115.40 (6)	C10—C11—H11B	109.3
C1—N1—C2	124.19 (5)	H11A—C11—H11B	108.0
C1—N1—C22	116.77 (5)	C13—C12—C17	118.43 (6)
C2—N1—C22	118.93 (5)	C13—C12—C11	120.52 (6)
C18—N2—C10	107.79 (5)	C17—C12—C11	121.01 (6)
O1—C1—N1	122.07 (6)	C12—C13—C14	120.55 (7)
O1—C1—C9	121.60 (5)	C12—C13—H13A	119.7
N1—C1—C9	116.00 (5)	C14—C13—H13A	119.7
O2—C2—N1	120.27 (6)	C15—C14—C13	120.51 (7)
O2—C2—C3	122.69 (6)	C15—C14—H14A	119.7
N1—C2—C3	116.99 (5)	C13—C14—H14A	119.7
C8—C3—C4	120.54 (6)	C16—C15—C14	119.32 (7)
C8—C3—C2	120.73 (5)	C16—C15—H15A	120.3
C4—C3—C2	118.72 (5)	C14—C15—H15A	120.3
C5—C4—C3	119.56 (6)	C15—C16—C17	120.25 (7)
C5—C4—H4A	120.2	C15—C16—H16A	119.9
C3—C4—H4A	120.2	C17—C16—H16A	119.9
C4—C5—C6	119.90 (6)	C16—C17—C12	120.90 (7)
C4—C5—H5A	120.0	C16—C17—H17A	119.6
C6—C5—H5A	120.0	C12—C17—H17A	119.6
C7—C6—C5	120.63 (6)	N2—C18—O3	118.47 (5)
C7—C6—H6A	119.7	N2—C18—C19	127.74 (6)
C5—C6—H6A	119.7	O3—C18—C19	113.79 (5)
C8—C7—C6	119.60 (6)	C18—C19—H19A	109.5
C8—C7—H7A	120.2	C18—C19—H19B	109.5
C6—C7—H7A	120.2	H19A—C19—H19B	109.5
C7—C8—C3	119.75 (5)	C18—C19—H19C	109.5
C7—C8—C9	121.41 (5)	H19A—C19—H19C	109.5
C3—C8—C9	118.72 (5)	H19B—C19—H19C	109.5
O3—C9—C8	109.49 (5)	O5—C20—O4	124.54 (6)
O3—C9—C1	107.97 (5)	O5—C20—C10	125.43 (6)
C8—C9—C1	112.93 (5)	O4—C20—C10	110.02 (5)
O3—C9—C10	102.22 (4)	O4—C21—H21A	109.5
C8—C9—C10	113.35 (5)	O4—C21—H21B	109.5
C1—C9—C10	110.23 (4)	H21A—C21—H21B	109.5
N2—C10—C20	110.16 (5)	O4—C21—H21C	109.5
N2—C10—C11	109.10 (5)	H21A—C21—H21C	109.5
C20—C10—C11	109.43 (5)	H21B—C21—H21C	109.5
N2—C10—C9	102.88 (4)	N1—C22—H22A	109.5
C20—C10—C9	109.71 (4)	N1—C22—H22B	109.5
C11—C10—C9	115.34 (5)	H22A—C22—H22B	109.5
C12—C11—C10	111.59 (5)	N1—C22—H22C	109.5
C12—C11—H11A	109.3	H22A—C22—H22C	109.5
C10—C11—H11A	109.3	H22B—C22—H22C	109.5
C2—N1—C1—O1	−165.85 (6)	C18—N2—C10—C20	−126.15 (5)
C22—N1—C1—O1	10.31 (9)	C18—N2—C10—C11	113.70 (6)
C2—N1—C1—C9	20.58 (8)	C18—N2—C10—C9	−9.25 (6)
C22—N1—C1—C9	−163.26 (5)	O3—C9—C10—N2	12.51 (5)
C1—N1—C2—O2	−178.23 (6)	C8—C9—C10—N2	−105.22 (5)
C22—N1—C2—O2	5.68 (9)	C1—C9—C10—N2	127.10 (5)
C1—N1—C2—C3	4.38 (9)	O3—C9—C10—C20	129.73 (5)
C22—N1—C2—C3	−171.70 (5)	C8—C9—C10—C20	12.00 (6)
O2—C2—C3—C8	170.61 (6)	C1—C9—C10—C20	−115.68 (5)
N1—C2—C3—C8	−12.07 (9)	O3—C9—C10—C11	−106.16 (5)
O2—C2—C3—C4	−10.41 (10)	C8—C9—C10—C11	136.11 (5)
N1—C2—C3—C4	166.91 (6)	C1—C9—C10—C11	8.43 (7)
C8—C3—C4—C5	1.63 (9)	N2—C10—C11—C12	66.89 (6)
C2—C3—C4—C5	−177.35 (6)	C20—C10—C11—C12	−53.70 (6)
C3—C4—C5—C6	−0.36 (10)	C9—C10—C11—C12	−177.96 (5)
C4—C5—C6—C7	−1.16 (10)	C10—C11—C12—C13	−80.98 (7)
C5—C6—C7—C8	1.40 (10)	C10—C11—C12—C17	96.54 (7)
C6—C7—C8—C3	−0.13 (9)	C17—C12—C13—C14	−1.85 (10)
C6—C7—C8—C9	−176.13 (6)	C11—C12—C13—C14	175.73 (6)
C4—C3—C8—C7	−1.38 (9)	C12—C13—C14—C15	0.33 (12)
C2—C3—C8—C7	177.58 (6)	C13—C14—C15—C16	1.25 (12)
C4—C3—C8—C9	174.72 (5)	C14—C15—C16—C17	−1.28 (11)
C2—C3—C8—C9	−6.31 (8)	C15—C16—C17—C12	−0.26 (11)
C18—O3—C9—C8	109.09 (5)	C13—C12—C17—C16	1.82 (10)
C18—O3—C9—C1	−127.60 (5)	C11—C12—C17—C16	−175.74 (6)
C18—O3—C9—C10	−11.36 (5)	C10—N2—C18—O3	2.44 (7)
C7—C8—C9—O3	−33.67 (7)	C10—N2—C18—C19	−177.79 (6)
C3—C8—C9—O3	150.29 (5)	C9—O3—C18—N2	6.70 (7)
C7—C8—C9—C1	−154.01 (6)	C9—O3—C18—C19	−173.11 (5)
C3—C8—C9—C1	29.96 (7)	C21—O4—C20—O5	3.34 (9)
C7—C8—C9—C10	79.73 (7)	C21—O4—C20—C10	−175.41 (5)
C3—C8—C9—C10	−96.30 (6)	N2—C10—C20—O5	7.11 (8)
O1—C1—C9—O3	28.45 (8)	C11—C10—C20—O5	127.05 (6)
N1—C1—C9—O3	−157.94 (5)	C9—C10—C20—O5	−105.46 (7)
O1—C1—C9—C8	149.65 (6)	N2—C10—C20—O4	−174.16 (5)
N1—C1—C9—C8	−36.74 (7)	C11—C10—C20—O4	−54.21 (6)
O1—C1—C9—C10	−82.44 (7)	C9—C10—C20—O4	73.27 (6)
N1—C1—C9—C10	91.17 (6)

D—H···A	D—H	H···A	D···A	D—H···A
C15—H15A···O5i	0.93	2.50	3.4311 (11)	179
C19—H19B···O5ii	0.96	2.43	3.2594 (11)	145
C22—H22A···O3iii	0.96	2.53	3.2479 (8)	132

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C15—H15A⋯O5i	0.93	2.50	3.4311 (11)	179
C19—H19B⋯O5ii	0.96	2.43	3.2594 (11)	145
C22—H22A⋯O3iii	0.96	2.53	3.2479 (8)	132

Symmetry codes: (i) ; (ii) ; (iii) .