rac-Ethyl 2-hy­droxy-2,7,7-trimethyl-4-(4-nitro­phen­yl)-5-oxo-3,4,5,6,7,8-hexa­hydro-2H-chromene-3-carboxyl­ate

Abel M Maharramov; Arif I Ismiev; Bahruz A Rashidov; Rizvan K Askerov; Konstantin A Potekhin

doi:10.1107/S1600536812050581

. 2012 Dec 15;69(Pt 1):o99. doi: 10.1107/S1600536812050581

rac-Ethyl 2-hydroxy-2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-3,4,5,6,7,8-hexahydro-2H-chromene-3-carboxylate

Abel M Maharramov ^a, Arif I Ismiev ^a, Bahruz A Rashidov ^a,^*, Rizvan K Askerov ^a, Konstantin A Potekhin ^b

PMCID: PMC3588292 PMID: 23476478

Abstract

The title molecule, C₂₁H₂₅NO₇, has four stereogenic centres and crystallized as a racemate. It consists of enantiomeric pairs with the relative configuration rac-(1R*,2S*,3R*). The cyclohexenone ring adopts an envelope conformation; the dimethyl-substituted C atom lies 0.640 (1) Å out of the mean plane formed by the rest of the ring atoms (r.m.s. deviation = 0.016 Å). The oxacyclohexene ring adopts a half-chair conformation, the hydroxy- and carboxyl-substituted C atoms lying −0.336 (1) and 0.419 (1) Å, respectively, out of the mean plane formed by the rest of the ring atoms (r.m.s. deviation = 0.002 Å). In the crystal, O—H⋯O hydrogen bonds link the molecules into a chain along the c-axis direction.

Related literature

For general background to 2H-chromenes and their derivatives, see: Cai (2008 ▶); Valenti et al. (1993 ▶); Hyana & Saimoto (1987 ▶); Tang et al. (2007 ▶). For their anticancer activity, see: Afantitis et al. (2006 ▶); Cai (2007 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₁H₂₅NO₇
M _r = 403.42
Monoclinic,
a = 10.4163 (8) Å
b = 24.2608 (18) Å
c = 8.0796 (6) Å
β = 96.437 (2)°
V = 2028.9 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 296 K
0.30 × 0.20 × 0.20 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1998 ▶) T _min = 0.971, T _max = 0.980
23423 measured reflections
5078 independent reflections
4084 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.118
S = 1.00
5078 reflections
266 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.30 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT-Plus (Bruker, 2005 ▶); data reduction: SAINT-Plus; 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.

Supplementary Material

Click here for additional data file.^{(22.3KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812050581/aa2078sup1.cif

e-69-00o99-sup1.cif^{(22.3KB, cif)}

Click here for additional data file.^{(248.7KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812050581/aa2078Isup2.hkl

e-69-00o99-Isup2.hkl^{(248.7KB, hkl)}

Click here for additional data file.^{(8.1KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812050581/aa2078Isup3.cml

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⋯O3ⁱ	0.82 (2)	2.08 (2)	2.8881 (15)	172 (2)

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Symmetry code: (i) Inline graphic .

Acknowledgments

We thank Baku State University and Vladimir State University for supporting this study.

supplementary crystallographic information

Comment

2H-chromenes and their derivatives possess various biological and pharmacological properties such as anti-viral, anti-fungal, anti-inflammatory, antidiabetic, cardionthonic, anti-anaphylactic and anti-cancer activity (Cai, 2008; Valenti et al., 1993; Hyana & Saimoto, 1987; Tang et al., 2007). 2H-chromenes are a new series of apoptosis inducers, which exhibit potent anticancer activity (Afantitis et al., 2006; Cai, 2007;). Considering the importance of 2H-chromene-3-carboxylate derivatives, a single-crystal X-ray diffraction study on the title compound was carried out and analyzed.

A simple synthesis of new and biologically active ethyl 2-hydroxy-2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-3,4,5,6,7,8-hexahydro-2H- chromene-3-carboxylate (Fig. 1) was carried out using cyclocondensation reaction of 4-nitrobenzaldehyde, acetoacetic ether and dimedone with allylamine as catalizator at room temperature. The title molecule is chiral with four stereogenic centres. The crystal is a racemate and consists of enantiomeric pairs with the relative configuration rac-(1R*, 2S*, 3R*). The cyclohexenone ring adopt a envelope conformation, C7 lies 0.640 (1) Å out of the plane formed by the rest of the ring atoms (r.m.s. deviation = 0.016 Å). The oxacyclohexene ring adopt a half-chair conformation, C1 and C2 lie -0.336 (1) and 0.419 (1) Å respectively out of the plane formed by the rest of the ring (r.m.s. deviation = 0.002 Å). The 4-nitrophenyl ring is in a pseudo-equatorial position. The torsion angle between the ethoxycarbonyl group and the 4-nirtophenyl substituent C11–C2–C3–C14 is -65.16 (13) ° that indicates the pseudo-axial location of hydrogen atoms at C2 and C3. Intermolecular O—H···O hydrogen bonds link molecules into a chain along the c axis (Table 1, Fig. 2).

Experimental

Dimedone (5 mmol), 4-nitrobenzaldehyde (5 mmol) and acetoacetic ether (5 mmol) were dissolved in ethanol (15 ml). Then allylamine (0.4 ml) was added and mixture was stirred at 300 K for 3 h. Obtained yellow crystals were filtered and washed with ethanol. The crystals were dissolved in ethanol (20 ml) and recrystallized to yield yellow crystals of the title compound suitable for X-ray analysis.