2-[4-(Piperidin-1-yl)-5H-chromeno[2,3-d]pyrimidin-2-yl]phenol

Naresh Sharma; Goutam Brahmachari; Suvankar Das; Rajni Kant; Vivek K Gupta

doi:10.1107/S1600536814005625

. 2014 Mar 15;70(Pt 4):o447–o448. doi: 10.1107/S1600536814005625

2-[4-(Piperidin-1-yl)-5H-chromeno[2,3-d]pyrimidin-2-yl]phenol

Naresh Sharma ^a, Goutam Brahmachari ^b, Suvankar Das ^b, Rajni Kant ^a, Vivek K Gupta ^a,^*

PMCID: PMC3998607 PMID: 24826150

Abstract

In the title compound, C₂₂H₂₁N₃O₂, the pyrimidine ring is essentially planar [maximum deviation = 0.018 (2) Å] and forms dihedral angles of 22.70 (8) and 0.97 (7)°, respectively, with the fused benzene ring and the hydroxy-substituted benzene ring. The piperidine ring has a chair conformation and the pyran ring has a flattened twist-boat conformation. The hydroxy group was refined as disordered over two sets of sites in a 0.702 (4):0.298 (4) ratio. The disorder corresponds to a rotation of approxomiately 180° about the C—C bond connecting the phenol group to the pyrimidine ring and hence, both the major and minor components of disorder form intramolecular O—H⋯N hydrogen bonds. In the crystal, pairs of weak C—H⋯π interactions form inversion dimers. In addition, π–π interactions are observed between the pyrimidine ring and the hydroxy-substituted benzene ring [centroid–centroid separation = 3.739 (2) Å].

Related literature

For applications of benzopyrano[2,3-d]pyrimidines, see: Hadfield et al. (1999 ▶); Bruno et al. (2001 ▶, 2004 ▶). For general background to benzopyrano[2,3-d]pyrimidines, see: Brahmachari & Das (2014 ▶). For a related structure, see: Gajera et al. (2013 ▶). For standard bond-length data, see: Allen et al. (1987 ▶). For conformational analysis, see: Duax & Norton (1975 ▶).

Experimental

Crystal data

C₂₂H₂₁N₃O₂
M _r = 359.42
Monoclinic,
a = 9.9826 (5) Å
b = 15.8773 (7) Å
c = 12.2197 (6) Å
β = 109.381 (6)°
V = 1827.03 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur Sapphire3 diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2010 ▶) T _min = 0.975, T _max = 0.983
13349 measured reflections
3576 independent reflections
1918 reflections with I > 2σ(I)
R _int = 0.048

Refinement

R[F ² > 2σ(F ²)] = 0.060
wR(F ²) = 0.133
S = 1.03
3576 reflections
254 parameters
12 restraints
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S1600536814005625/lh5695sup1.cif

e-70-0o447-sup1.cif^{(28.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814005625/lh5695Isup2.hkl

e-70-0o447-Isup2.hkl^{(171.8KB, hkl)}

Click here for additional data file.^{(7.4KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814005625/lh5695Isup3.cml

CCDC reference: 975917

Additional supporting information: crystallographic information; 3D view; checkCIF report

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

Cg is the centroid of the C6–C9/C12/C13 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O27A—H27A⋯N3	0.82	1.78	2.535 (3)	151
O27B—H27B⋯N1	0.82	1.83	2.551 (3)	146
C5—H5B⋯Cg ⁱ	0.97	2.67	3.59	159

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Symmetry code: (i) Inline graphic .

Acknowledgments

RK acknowledges the Department of Science & Technology for the single-crystal X-ray diffractometer sanctioned as a National Facility under project No. SR/S2/CMP-47/2003. GB is thankful to the CSIR, New Delhi, for financial support [grant No. 02 (110)/12/EMR-II]. SD is grateful to the UGC, New Delhi, for the award of a Junior Research Fellowship.

supplementary crystallographic information

1. Comment

Benzopyrano[2,3-d]pyrimidines have gained much attention as significant medicinal scaffolds due to their inherent and multidirectional pharmaceutical potentials that include anti-inflammatory, analgesic, and anti-aggregating activities (Bruno et al., 2001,2004). More importantly, such chemical entities have been found to exhibit potent in vivo antitumor as well as in vitro cytotoxic activity against various cancer cell lines causing considerable degree of perturbation in cell cycle kinetics (Hadfield et al., 1999). Very recently, we have developed a straight forward and efficient pseudo four-component one-pot synthesis of diverse benzopyrano[2,3-d]pyrimidine scaffolds in good yields using commercially available sodium formate as an inexpensive and non-toxic catalyst (Brahmachari & Das, 2014). Herein, we wish to report the environmentally benign one-pot synthesis and X-ray crystal structure of 2-(4-(piperidin-1-yl)-5H-chromeno[2,3-d]pyrimidin-2-yl)phenol.

The molecular structure of the title compound (I) is shown in Fig. 1. In (I), the expected values for the bond-lengths are observed (Allen et al., 1987) and the distances are comparable to a closely related structure (Gajera et al., 2013). The pyrimidine ring (A) is essentially planar with a maximum deviation of 0.019 (2) Å for C4. This ring forms dihedral angles of 22.70 (8)° and 0.97 (7)°, respectively, with the fused benzene ring (B) and hydroxy-substituted benzene ring (E). The pyran ring (C) adopts a flattened twist-boat conformation with asymmetry parameters [ΔCs(C5—C10)=2.61, ΔC2(C11—C14)=2.66] and the piperidine ring (D) adopts chair conformation with asymmetry parameters [ΔCs(C17—C20)=2.67, ΔC2(C17—C8)=0.2] (Duax & Norton, 1975). The hydroxy group was refined as disordered over two sets of sites in a 0.702 (4): 0.298 (4) ratio. The disorder corresponds to a rotation of approxomiately 180° about the C2—C21 bond and hence, both the major and minor components of disorder form intramolecular O—H···N hydrogen bonds (see Table 1). In the crystal, pairs of weak C—H···π interactions form inversion dimers. In addition, π–π interactions are observed between the pyrimidine ring and hydroxy-substituted benzene ring [centroid–centroid seperation = 3.739 (2) Å, interplanar spacing = 3.534 Å, centriod shift = 1.22 Å, symmetry code: 1 - x,1 - y,1 - z]. The crystal packing is shown in Fig. 2.

2. Experimental

Infrared spectra were recorded using a Shimadzu (FT—IR 8400S) FT—IR spectrophotometer using KBr disc. 1H and 13 C NMR spectra was obtained at 400 and 100 MHz, respectively, using Bruker DRX spectrometer and CDCl₃ and DMSO-d6 as solvents. Elemental analysis was performed with an Elementar Vario EL III Carlo Erba 1108 micro-analyzer instrument. Melting point was recorded on a Sunvic melting point apparatus and is uncorrected. TLC was performed using silica gel 60 F254 (Merck) plates. An oven-dried screw cap test tube was charged with a magnetic stir bar, salicylaldehyde (2 mmol), malononitrile (1 mmol), piperidine (1 mmol), and sodium formate (10 mol%) in 4 ml e thanol. The reaction mixture was stirred at room temperature for 12 h. On completion of the reaction as monitored by TLC, the product was precipitated out and filtered; the filtrate was preserved for reuse. The crude residue was washed with water followed by ethanol to obtain pure product 1, characterized by elemental analyses as well as spectral studies including FT—IR, 1H-NMR and 13 C-NMR. The title compound (50 mg) was dissolved in 10 ml DMSO and left for several days at ambient temperature which yielded single crystals suitable for X-ray diffraction.