1′-Benzylspiro­[chromene-2,4′-piperi­dine]-4-carbonitrile

P Rajalakshmi; N Srinivasan; R V Krishnakumar

doi:10.1107/S1600536812035568

. 2012 Aug 23;68(Pt 9):o2732. doi: 10.1107/S1600536812035568

1′-Benzylspiro[chromene-2,4′-piperidine]-4-carbonitrile

P Rajalakshmi ^a, N Srinivasan ^a,^*, R V Krishnakumar ^a

PMCID: PMC3435744 PMID: 22969615

Abstract

In the title compound, C₂₁H₂₀N₂O, the piperidine ring adopts a chair conformation while the pyran ring adopts a screw-boat conformation. The piperidine ring forms dihedral angles of 65.75 (3) and 67.79 (5)° with the chroman and methyl-substituted benzene rings, respectively. The crystal structure features weak C—H⋯π and π–π [centroid–centroid distance = 3.8098 (8) Å] interactions.

Related literature

For the biological activity of piperidinecarbonitrile derivatives, see: Cardellicchio et al. (2010 ▶); Huang et al. (2008 ▶); Kumar et al. (2010 ▶); Arbiser et al. (2007 ▶). For uses of piperidinecarbonitrile derivatives, see: Barth et al. (2005 ▶); Vicente (2001 ▶); Terasaki et al. (2003 ▶). For industrial applications, see: Eller et al. (2002 ▶). For puckering prameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₁H₂₀N₂O
M _r = 316.39
Monoclinic,
a = 15.1666 (9) Å
b = 10.0472 (6) Å
c = 12.4360 (8) Å
β = 113.931 (2)°
V = 1732.11 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 298 K
0.35 × 0.30 × 0.25 mm

Data collection

Bruker Kappa APEXII diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2008 ▶) T _min = 0.974, T _max = 0.981
24973 measured reflections
6238 independent reflections
3363 reflections with I > 2σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.049
wR(F ²) = 0.152
S = 1.01
6238 reflections
217 parameters
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLUTON (Spek, 2009) ▶; software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812035568/gw2123sup1.cif

e-68-o2732-sup1.cif^{(25.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812035568/gw2123Isup2.hkl

e-68-o2732-Isup2.hkl^{(299.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812035568/gw2123Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 is the centroid of the C15–C20 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯Cg1ⁱ	0.93	2.95	3.7587 (15)	146

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Dr Babu Vargheese, SAIF, IIT-Madras, India, for the data collection.

supplementary crystallographic information

Comment

Piperidine carbonitrile derivatives are used as sensitizers in photodynamic therapy (PDT) (Vicente, 2001) and in boron neutron capture therapy (BNCT) (Barth et al., 2005) of brain tumors, which protects the central nervous system from drugs and endogenous molecules (Terasaki et al., 2003) and exhibits good bioactivities (Cardellicchio et al. 2010; Huang et al. 2008; Kumar et al. 2010). Also, piperidines find application in the production of dipiperidinyl dithiuram tetrasulfide which is used as a rubber vulcanization accelerator (Eller et al. 2002). The piperidine structural motif is present in natural alkaloids of fire ant toxin solenopsin and is an inhibitor of phosphatidylinositol-3-kinase signalling and angiogenesis (Arbiser et al. 2007).

In the title molecule (Fig. 1), the puckering conformation (Cremer & Pople, 1975) of the pyran ring (C8/C7/C2/O1/C1/C9) is nearly screw boat (⁵S₄) with parameters: Q = 0.3407 (12) Å, θ = 116.2 (2)° and φ = 213.0 (2)°. The deviation of O1 and C1 from the mean plane defined by the rest of the atoms is -0.6934 Å and 0.6178 Å, respectively. The puckering of the piperidine ring (N2/C10/C11/C1/C12/C13) with parameters of Q = 0.5660 (14) Å, θ = 173.13 (13) ° and φ = 181.5 (12) ° is close to ideal chair (¹C₄) and the deviations of N2 and C1 from the mean plane defined by the rest of the atoms by -0.6934 (16) Å and 0.6178 (17) Å, respectively.

The crystal structure of the title compound demonstrates the importance of weak interactions in optimizing the molecular aggregation in crystals. With the lone acceptor oxygen O1 unavailable for participation in intermolecular interactions for sterical reasons, the weak C–H···π and π···π interactions assume significance. A C3—H3···Cg1 (1 - x, 1/2 + y, 1/2 - z), Cg1 being the centroid of the benzene ring defined by C15 – C20, having a distance of 2.95 Å and angle of 146°, generates chains running along the b axis. A Cg2··· Cg2 (-x + 1, y + 1/2, -z + 1/2) interaction, Cg2 being the centroid of the benzene ring defined by C2 – C7, observed between two benzene rings of the chroman. The corresponding ring-centroid separation is 3.8098 (8) Å, with an interplanar spacing of ca 3.51 Å and a ring offset of ca 1.48 Å. These interactions generate a π-stacked extended sheets running parallel to the [011] direction (Fig. 3).

The accurate description of the crystal structure of title compound is of interest due to the absence of conventional hydrogen bonding and thus gains importance in the context of crystal structure prediction. Precise single-crystal X-ray investigations on similar compounds might throw light on the delicate nature of intermolecular interactions.

Experimental

Trimethylsilylcyanide (1.2 mmol) was added to a mixture of 1'1'-benzyl-3, 4-dihydrospiro [1-benzopyran-2, 4'- piperidine]-4-one (1.0 mmol) and catalytic amount of ZnI₂ in dichloromethane (10 vol), under a nitrogen atmosphere. The reaction mixture was stirred at 50°C for 6 h and then cooled to room temperature, dilute HCl (5 ml) was added and stirring continued for additional 2 h. The solution was extracted with ethylacetate (20 ml), dried over Na₂SO₄ and evaporated to dryness. The crude product was dissolved in benzene (10 ml), to which tosic acid (0.1 mmol) had been added and the solution was heated to reflux for 2 h. After completion of the reaction as indicated by TLC, the reaction mixture was concentrated under reduced pressure. The residue was diluted with ethylacetate (20 ml), washed with bicarbonate solution (10 ml) dried and concentrated. The crude product was purified by column chromatography to provide the desired product as colorless solid. Crystals of the title compound were grown from its solution in ethanol by slow evaporation at room temperature.