13-Hydr-oxy-4,16-dimethyl-4,16-diaza-penta-cyclo-[12.3.1.0.0.0]octa-deca-7(12),8,10-triene-6,18-dione.

In the title compound, C(18)H(20)N(2)O(3), the N-methyl-piperidone ring adopts a chair conformation. The pyrrolidine ring and the five-membered cyclo-pentane rings adopt envelope conformations. The five-membered ring of the ninhydrin system adopts an envelope conformation with the central C atom deviating by 0.217 (1)Å from the mean plane through the other atoms. The mol-ecular packing is characterized by inter-molecular C-H⋯O and intra-molecular C-H⋯O and O-H⋯N inter-actions.

Related literature

For the cytotoxic and anti­cancer properties of piperidinones, see: Dimmock et al. (1990 ▶, 2001 ▶). Piperidinone derivatives have attracted attention due to their predicted mode of inter­action with cellular thiols, having little or no affinity for the hydr­oxy and amino groups found in nucleic acids, see: Baluja et al. (1964 ▶); Mutus et al. (1989 ▶). Ninhydrin is used to monitor deprotection in solid phase peptide synthesis (Kaiser et al., 1970 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C18H20N2O3

M = 312.36

Monoclinic,

a = 11.0862 (5) Å

b = 11.6152 (5) Å

c = 12.5670 (6) Å

β = 102.851 (9)°

V = 1577.70 (12) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 293 K

0.18 × 0.13 × 0.11 mm

Data collection

Nonius MACH-3 diffractometer

Absorption correction: ψ scan (North et al., 1968 ▶) T min = 0.984, T max = 0.990

3226 measured reflections

2764 independent reflections

1978 reflections with I > 2σ(I)

R int = 0.046

2 standard reflections frequency: 60 min intensity decay: none

Refinement

R[F 2 > 2σ(F 2)] = 0.039

wR(F 2) = 0.120

S = 1.04

2764 reflections

211 parameters

H-atom parameters constrained

Δρmax = 0.16 e Å−3

Δρmin = −0.18 e Å−3

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ▶); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1996 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809015293/at2770sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809015293/at2770Isup2.hkl

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

C18H20N2O3	F(000) = 664
Mr = 312.36	Dx = 1.315 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 25 reflections
a = 11.0862 (5) Å	θ = 2–25°
b = 11.6152 (5) Å	µ = 0.09 mm−1
c = 12.5670 (6) Å	T = 293 K
β = 102.851 (9)°	Needle, colourless
V = 1577.70 (12) Å3	0.18 × 0.13 × 0.11 mm
Z = 4

Nonius MACH-3 diffractometer	1978 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.046
graphite	θmax = 25.0°, θmin = 2.2°
ω–2θ scans	h = 0→13
Absorption correction: ψ scan (North et al., 1968)	k = −1→13
Tmin = 0.984, Tmax = 0.990	l = −14→14
3226 measured reflections	2 standard reflections every 60 min
2764 independent reflections	intensity decay: none

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)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.120	H-atom parameters constrained
S = 1.04	w = 1/[σ2(Fo2) + (0.0616P)2 + 0.2971P] where P = (Fo2 + 2Fc2)/3
2764 reflections	(Δ/σ)max < 0.001
211 parameters	Δρmax = 0.16 e Å−3
0 restraints	Δρmin = −0.18 e Å−3

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.

	x	y	z	Uiso*/Ueq
C1	0.37990 (16)	0.05350 (16)	0.64487 (16)	0.0558 (5)
C2	0.25684 (15)	0.03912 (14)	0.56351 (16)	0.0496 (4)
C3	0.15940 (16)	0.06258 (15)	0.63055 (15)	0.0517 (4)
H3A	0.0772	0.0460	0.5874	0.062*
H3B	0.1744	0.0143	0.6951	0.062*
C4	0.39217 (16)	0.18110 (16)	0.66421 (15)	0.0537 (5)
H4	0.4750	0.2026	0.7051	0.064*
C5	0.29116 (17)	0.21625 (17)	0.72388 (14)	0.0554 (5)
H5A	0.3067	0.1796	0.7950	0.067*
H5B	0.2935	0.2989	0.7349	0.067*
C6	0.36690 (14)	0.22296 (15)	0.54459 (15)	0.0471 (4)
C7	0.26099 (14)	0.14067 (15)	0.48444 (13)	0.0461 (4)
C8	0.14614 (15)	0.21810 (16)	0.45590 (13)	0.0471 (4)
C9	0.18837 (16)	0.33902 (15)	0.47548 (14)	0.0475 (4)
C10	0.31366 (16)	0.34242 (15)	0.52472 (14)	0.0472 (4)
C11	0.37277 (19)	0.44677 (16)	0.54870 (16)	0.0595 (5)
H11	0.4564	0.4498	0.5824	0.071*
C12	0.3053 (2)	0.54695 (17)	0.52175 (17)	0.0680 (6)
H12	0.3445	0.6178	0.5363	0.082*
C13	0.1808 (2)	0.54309 (18)	0.47352 (17)	0.0688 (6)
H13	0.1369	0.6114	0.4570	0.083*
C14	0.12088 (19)	0.43966 (18)	0.44954 (16)	0.0602 (5)
H14	0.0370	0.4372	0.4167	0.072*
C15	0.24197 (18)	−0.07110 (18)	0.49582 (19)	0.0671 (6)
H15A	0.3119	−0.1222	0.5203	0.080*
H15B	0.1667	−0.1113	0.5006	0.080*
C16	0.2361 (2)	−0.0302 (2)	0.3805 (2)	0.0798 (7)
H16A	0.2811	−0.0824	0.3431	0.096*
H16B	0.1509	−0.0260	0.3397	0.096*
C17	0.2705 (2)	0.1496 (2)	0.28884 (17)	0.0845 (7)
H17A	0.1830	0.1563	0.2602	0.127*
H17B	0.3075	0.1103	0.2369	0.127*
H17C	0.3061	0.2249	0.3025	0.127*
C18	0.06767 (19)	0.2233 (2)	0.70672 (18)	0.0693 (6)
H18A	−0.0089	0.2123	0.6544	0.104*
H18B	0.0787	0.3036	0.7240	0.104*
H18C	0.0660	0.1808	0.7719	0.104*
N1	0.16914 (13)	0.18280 (12)	0.66132 (11)	0.0479 (4)
N2	0.29314 (14)	0.08429 (15)	0.39070 (13)	0.0603 (4)
O1	0.04209 (10)	0.18577 (12)	0.41422 (11)	0.0618 (4)
O2	0.47670 (10)	0.20956 (13)	0.50608 (13)	0.0650 (4)
H2	0.4673	0.1578	0.4606	0.098*
O3	0.45072 (13)	−0.02185 (13)	0.68415 (14)	0.0810 (5)

	U11	U22	U33	U12	U13	U23
C1	0.0474 (10)	0.0498 (11)	0.0671 (12)	0.0042 (8)	0.0059 (9)	0.0104 (9)
C2	0.0446 (9)	0.0392 (9)	0.0636 (11)	−0.0012 (7)	0.0093 (8)	−0.0055 (8)
C3	0.0506 (10)	0.0463 (10)	0.0576 (11)	−0.0046 (8)	0.0110 (8)	0.0019 (8)
C4	0.0431 (9)	0.0535 (11)	0.0569 (11)	−0.0048 (8)	−0.0055 (8)	0.0016 (9)
C5	0.0653 (11)	0.0536 (11)	0.0430 (9)	−0.0058 (9)	0.0026 (8)	0.0004 (8)
C6	0.0342 (8)	0.0477 (10)	0.0585 (10)	−0.0011 (7)	0.0082 (7)	0.0006 (8)
C7	0.0390 (9)	0.0495 (10)	0.0493 (10)	−0.0009 (7)	0.0089 (7)	−0.0065 (8)
C8	0.0395 (9)	0.0594 (11)	0.0416 (9)	0.0023 (8)	0.0073 (7)	0.0001 (8)
C9	0.0505 (10)	0.0509 (10)	0.0434 (9)	0.0056 (8)	0.0150 (7)	0.0053 (8)
C10	0.0504 (10)	0.0472 (10)	0.0463 (9)	−0.0013 (8)	0.0155 (8)	0.0038 (8)
C11	0.0648 (12)	0.0516 (12)	0.0635 (12)	−0.0107 (9)	0.0171 (9)	0.0023 (9)
C12	0.0982 (17)	0.0463 (12)	0.0655 (13)	−0.0053 (11)	0.0311 (12)	0.0055 (10)
C13	0.0958 (17)	0.0522 (13)	0.0640 (13)	0.0185 (11)	0.0300 (12)	0.0143 (10)
C14	0.0639 (12)	0.0639 (13)	0.0544 (11)	0.0184 (10)	0.0168 (9)	0.0104 (9)
C15	0.0553 (11)	0.0494 (11)	0.0965 (16)	−0.0015 (9)	0.0170 (11)	−0.0161 (11)
C16	0.0767 (15)	0.0750 (16)	0.0899 (17)	−0.0090 (11)	0.0229 (12)	−0.0364 (13)
C17	0.0865 (16)	0.117 (2)	0.0548 (13)	0.0058 (14)	0.0251 (11)	−0.0107 (13)
C18	0.0730 (13)	0.0697 (14)	0.0681 (13)	0.0075 (11)	0.0222 (10)	−0.0097 (11)
N1	0.0508 (8)	0.0466 (8)	0.0461 (8)	−0.0003 (6)	0.0105 (6)	−0.0013 (6)
N2	0.0567 (9)	0.0692 (11)	0.0584 (10)	0.0002 (8)	0.0201 (7)	−0.0161 (8)
O1	0.0403 (7)	0.0767 (10)	0.0626 (8)	−0.0001 (6)	−0.0011 (6)	−0.0024 (7)
O2	0.0405 (7)	0.0683 (10)	0.0891 (11)	−0.0026 (6)	0.0207 (6)	−0.0079 (8)
O3	0.0642 (9)	0.0617 (9)	0.1068 (13)	0.0116 (7)	−0.0029 (8)	0.0202 (8)

C1—O3	1.206 (2)	C10—C11	1.379 (3)
C1—C4	1.503 (3)	C11—C12	1.384 (3)
C1—C2	1.521 (2)	C11—H11	0.9300
C2—C15	1.526 (3)	C12—C13	1.379 (3)
C2—C3	1.535 (3)	C12—H12	0.9300
C2—C7	1.549 (3)	C13—C14	1.374 (3)
C3—N1	1.446 (2)	C13—H13	0.9300
C3—H3A	0.9700	C14—H14	0.9300
C3—H3B	0.9700	C15—C16	1.513 (3)
C4—C5	1.535 (3)	C15—H15A	0.9700
C4—C6	1.545 (3)	C15—H15B	0.9700
C4—H4	0.9800	C16—N2	1.466 (3)
C5—N1	1.458 (2)	C16—H16A	0.9700
C5—H5A	0.9700	C16—H16B	0.9700
C5—H5B	0.9700	C17—N2	1.461 (3)
C6—O2	1.415 (2)	C17—H17A	0.9600
C6—C10	1.507 (2)	C17—H17B	0.9600
C6—C7	1.571 (2)	C17—H17C	0.9600
C7—N2	1.460 (2)	C18—N1	1.448 (2)
C7—C8	1.535 (2)	C18—H18A	0.9600
C8—O1	1.2154 (19)	C18—H18B	0.9600
C8—C9	1.484 (3)	C18—H18C	0.9600
C9—C14	1.387 (3)	O2—H2	0.8200
C9—C10	1.390 (2)
O3—C1—C4	128.48 (17)	C11—C10—C6	128.58 (16)
O3—C1—C2	126.90 (18)	C9—C10—C6	111.31 (14)
C4—C1—C2	104.62 (14)	C10—C11—C12	118.75 (19)
C1—C2—C15	115.87 (15)	C10—C11—H11	120.6
C1—C2—C3	104.30 (15)	C12—C11—H11	120.6
C15—C2—C3	116.94 (15)	C13—C12—C11	120.90 (19)
C1—C2—C7	101.38 (13)	C13—C12—H12	119.6
C15—C2—C7	107.23 (16)	C11—C12—H12	119.6
C3—C2—C7	109.99 (14)	C14—C13—C12	120.86 (19)
N1—C3—C2	107.36 (14)	C14—C13—H13	119.6
N1—C3—H3A	110.2	C12—C13—H13	119.6
C2—C3—H3A	110.2	C13—C14—C9	118.43 (19)
N1—C3—H3B	110.2	C13—C14—H14	120.8
C2—C3—H3B	110.2	C9—C14—H14	120.8
H3A—C3—H3B	108.5	C16—C15—C2	104.31 (17)
C1—C4—C5	106.95 (15)	C16—C15—H15A	110.9
C1—C4—C6	99.36 (15)	C2—C15—H15A	110.9
C5—C4—C6	113.42 (14)	C16—C15—H15B	110.9
C1—C4—H4	112.1	C2—C15—H15B	110.9
C5—C4—H4	112.1	H15A—C15—H15B	108.9
C6—C4—H4	112.1	N2—C16—C15	105.95 (17)
N1—C5—C4	110.85 (14)	N2—C16—H16A	110.5
N1—C5—H5A	109.5	C15—C16—H16A	110.5
C4—C5—H5A	109.5	N2—C16—H16B	110.5
N1—C5—H5B	109.5	C15—C16—H16B	110.5
C4—C5—H5B	109.5	H16A—C16—H16B	108.7
H5A—C5—H5B	108.1	N2—C17—H17A	109.5
O2—C6—C10	112.31 (14)	N2—C17—H17B	109.5
O2—C6—C4	108.33 (14)	H17A—C17—H17B	109.5
C10—C6—C4	115.51 (15)	N2—C17—H17C	109.5
O2—C6—C7	112.10 (14)	H17A—C17—H17C	109.5
C10—C6—C7	104.91 (13)	H17B—C17—H17C	109.5
C4—C6—C7	103.35 (13)	N1—C18—H18A	109.5
N2—C7—C8	114.40 (14)	N1—C18—H18B	109.5
N2—C7—C2	102.91 (14)	H18A—C18—H18B	109.5
C8—C7—C2	117.03 (14)	N1—C18—H18C	109.5
N2—C7—C6	111.76 (13)	H18A—C18—H18C	109.5
C8—C7—C6	104.37 (14)	H18B—C18—H18C	109.5
C2—C7—C6	106.28 (13)	C3—N1—C18	113.60 (15)
O1—C8—C9	126.74 (16)	C3—N1—C5	113.99 (14)
O1—C8—C7	125.32 (17)	C18—N1—C5	114.19 (15)
C9—C8—C7	107.53 (13)	C7—N2—C17	116.69 (17)
C14—C9—C10	120.94 (17)	C7—N2—C16	107.45 (16)
C14—C9—C8	128.68 (16)	C17—N2—C16	114.03 (18)
C10—C9—C8	110.36 (14)	C6—O2—H2	109.5
C11—C10—C9	120.10 (17)
O3—C1—C2—C15	−22.8 (3)	C6—C7—C8—O1	−175.36 (16)
C4—C1—C2—C15	157.13 (17)	N2—C7—C8—C9	−110.88 (16)
O3—C1—C2—C3	107.2 (2)	C2—C7—C8—C9	128.67 (15)
C4—C1—C2—C3	−72.83 (18)	C6—C7—C8—C9	11.57 (17)
O3—C1—C2—C7	−138.5 (2)	O1—C8—C9—C14	−1.2 (3)
C4—C1—C2—C7	41.44 (18)	C7—C8—C9—C14	171.71 (17)
C1—C2—C3—N1	66.97 (17)	O1—C8—C9—C10	−179.96 (17)
C15—C2—C3—N1	−163.63 (15)	C7—C8—C9—C10	−7.01 (19)
C7—C2—C3—N1	−41.05 (18)	C14—C9—C10—C11	0.1 (3)
O3—C1—C4—C5	−112.9 (2)	C8—C9—C10—C11	178.94 (16)
C2—C1—C4—C5	67.20 (18)	C14—C9—C10—C6	−179.82 (16)
O3—C1—C4—C6	129.0 (2)	C8—C9—C10—C6	−1.0 (2)
C2—C1—C4—C6	−50.92 (17)	O2—C6—C10—C11	−49.6 (2)
C1—C4—C5—N1	−56.50 (19)	C4—C6—C10—C11	75.3 (2)
C6—C4—C5—N1	52.0 (2)	C7—C6—C10—C11	−171.64 (18)
C1—C4—C6—O2	−80.09 (16)	O2—C6—C10—C9	130.29 (15)
C5—C4—C6—O2	166.74 (14)	C4—C6—C10—C9	−104.79 (17)
C1—C4—C6—C10	152.95 (14)	C7—C6—C10—C9	8.28 (18)
C5—C4—C6—C10	39.8 (2)	C9—C10—C11—C12	−0.7 (3)
C1—C4—C6—C7	38.98 (16)	C6—C10—C11—C12	179.21 (17)
C5—C4—C6—C7	−74.19 (17)	C10—C11—C12—C13	1.1 (3)
C1—C2—C7—N2	102.34 (15)	C11—C12—C13—C14	−0.9 (3)
C15—C2—C7—N2	−19.57 (17)	C12—C13—C14—C9	0.3 (3)
C3—C2—C7—N2	−147.71 (14)	C10—C9—C14—C13	0.1 (3)
C1—C2—C7—C8	−131.31 (15)	C8—C9—C14—C13	−178.51 (17)
C15—C2—C7—C8	106.79 (17)	C1—C2—C15—C16	−113.14 (18)
C3—C2—C7—C8	−21.4 (2)	C3—C2—C15—C16	123.18 (18)
C1—C2—C7—C6	−15.26 (17)	C7—C2—C15—C16	−0.81 (19)
C15—C2—C7—C6	−137.16 (14)	C2—C15—C16—N2	21.1 (2)
C3—C2—C7—C6	94.70 (15)	C2—C3—N1—C18	168.67 (15)
O2—C6—C7—N2	−9.8 (2)	C2—C3—N1—C5	−58.18 (19)
C10—C6—C7—N2	112.33 (16)	C4—C5—N1—C3	53.1 (2)
C4—C6—C7—N2	−126.26 (15)	C4—C5—N1—C18	−174.04 (16)
O2—C6—C7—C8	−133.98 (15)	C8—C7—N2—C17	35.0 (2)
C10—C6—C7—C8	−11.83 (17)	C2—C7—N2—C17	163.01 (16)
C4—C6—C7—C8	109.58 (15)	C6—C7—N2—C17	−83.3 (2)
O2—C6—C7—C2	101.72 (16)	C8—C7—N2—C16	−94.49 (19)
C10—C6—C7—C2	−136.13 (14)	C2—C7—N2—C16	33.53 (18)
C4—C6—C7—C2	−14.72 (16)	C6—C7—N2—C16	147.18 (16)
N2—C7—C8—O1	62.2 (2)	C15—C16—N2—C7	−35.3 (2)
C2—C7—C8—O1	−58.3 (2)	C15—C16—N2—C17	−166.26 (17)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···N2	0.82	2.12	2.655 (2)	123
C15—H15A···O3	0.97	2.56	2.974 (3)	106
C18—H18B···O3i	0.96	2.39	3.288 (3)	155

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯N2	0.82	2.12	2.655 (2)	123
C18—H18B⋯O3i	0.96	2.39	3.288 (3)	155

Symmetry code: (i) .