13-Hydr­oxy-4,16-dimethyl-4,16-diaza­penta­cyclo­[12.3.1.01,5.05,13.07,12]octa­deca-7(12),8,10-triene-6,18-dione

J Suresh; K Gurunathan; R Suresh Kumar; S Perumal; P L Nilantha Lakshman

doi:10.1107/S1600536809015293

. 2009 Apr 30;65(Pt 5):o1163–o1164. doi: 10.1107/S1600536809015293

13-Hydroxy-4,16-dimethyl-4,16-diazapentacyclo[12.3.1.0^1,5.0^5,13.0^7,12]octadeca-7(12),8,10-triene-6,18-dione

J Suresh ^a, K Gurunathan ^a, R Suresh Kumar ^b, S Perumal ^b, P L Nilantha Lakshman ^c,^*

PMCID: PMC2977829 PMID: 21583966

Abstract

In the title compound, C₁₈H₂₀N₂O₃, the N-methylpiperidone ring adopts a chair conformation. The pyrrolidine ring and the five-membered cyclopentane 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 molecular packing is characterized by intermolecular C—H⋯O and intramolecular C—H⋯O and O—H⋯N interactions.

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 _r = 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
Δρ_max = 0.16 e Å⁻³
Δρ_min = −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.

Supplementary Material

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

e-65-o1163-sup1.cif^{(21.8KB, cif)}

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

e-65-o1163-Isup2.hkl^{(133KB, hkl)}

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

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

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Symmetry code: (i) Inline graphic .

Acknowledgments

JS and SG thank the Management of The Madura College, Madurai, for their constant support.

supplementary crystallographic information

Comment

Piperidinones belong to an important class of heterocycles which are found to possess a variety of biological activities, including cytotoxic and anticancer properties (Dimmock et al., 1990, 2001). Derivatives of piperidinones have also attracted wide attention from chemists and biologists 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 (Baluja et al., 1964; Mutus et al., 1989). Ninhydrin is used to monitor deprotection in solid phase peptide synthesis (Kaiser et al., 1970).

The molecular structure of the title compound is shown in Fig.1. The n-methyl piperidone ring adopts a chair conformation [Q=0.6668 (19) Å, θ= 13.62 (16)°, Φ= 152.0 (7)°; Cremer and Pople, 1975]. The pyrrolidine ring A(N2—C16) and the five membered cyclopentane ring B(C1—C4) adopt envelope conformations [puckering parameters Q=0.327 (2) Å, Φ=178.8 (4)° and Q=0.483 (2) Å, Φ=162.3 (2)° respectively, Cremer and Pople, 1975]. In the ninhydrin system, in the five membered ring the flap atom C7 deviate from the mean plane formed by other atoms C6/C8/C9/C10/C11/C12/C13/C14 by 0.217 (1)Å adopting an envelope conformation. The sum of the angle at the atom N2 is 338.17 (2)° is in accordance with sp³ hybridization.

Fig. 2 shows the packing viewed down the c—axis. The molecular interaction through C—H···O (Table 1) hydrogen bonds, generating a graph set motif of C₁¹(7) along the b—axis, stabilize the crystal structure. There are neither a marked C—H···π nor π···π interactions in the structure.

Experimental

A mixture of 1-methyl-4-piperidinone 0.200 g (0.002 mol), ninhydrin 0.315 g (0.002 mol) and sarcosine 0.156 g (0.002 mol) in methanol (30 ml) were refluxed in a water bath for 10 h. After completion of the reaction as monitored by TLC, the excess solvent was removed under vacuum and the residue subjected to flash column chromatography using petroleum ether:ethyl acetate mixture (8:2 v/v) as eluent to obtain crystals of title compound in 8% yield along with a other product. Yield: 8%, melting point: 435–436 K.