c-5-Hy­droxy-r-2,c-4-bis­(meth­oxy­carbon­yl)-t-5-methyl-t-3-(3-nitro­phen­yl)cyclo­hexa­none

S Rizwana Begum; R Hema; K Pandiarajan; Sridhar Balasubramanian; AG Anitha

doi:10.1107/S1600536812027377

. 2012 Jun 27;68(Pt 7):o2213. doi: 10.1107/S1600536812027377

c-5-Hydroxy-r-2,c-4-bis(methoxycarbonyl)-t-5-methyl-t-3-(3-nitrophenyl)cyclohexanone

S Rizwana Begum ^a, R Hema ^a,^*, K Pandiarajan ^b, Sridhar Balasubramanian ^c, AG Anitha ^a

PMCID: PMC3394008 PMID: 22798873

Abstract

In the title compound, C₁₇H₁₉NO₈ [systematic name = dimethyl 4-hydroxy-4-methyl-2-(3-nitrophenyl)-6-oxocyclohexane-1,3-dicarboxylate], the cyclohexanone ring exhibits a chair conformation. The methoxycarbonyl groups are oriented in opposite directions with respect to the cyclohexanone ring. In the crystal, O—H⋯O hydrogen bonds links the molecules into chains running parallel to the a axis. These chains are connected by weak C—H⋯O hydrogen bonds, forming sheets parallel to the ab plane.

Related literature

For the pharmacological activity of cyclohexanone derivatives, see: Puetz et al.(2003 ▶); Danyi et al. (1989 ▶); For related structure, see: Hema et al. (2006 ▶). For conformational analysis, see: Allinger (1977 ▶); Cremer & Pople (1975 ▶). For graph-set analysis, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₁₇H₁₉NO₈
M _r = 365.33
Monoclinic,
a = 20.1842 (18) Å
b = 5.7380 (5) Å
c = 15.5771 (14) Å
β = 108.357 (1)°
V = 1712.3 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 273 K
0.3 × 0.18 × 0.15 mm

Data collection

Bruker SMART CCD area-detector diffractometer
7818 measured reflections
1513 independent reflections
1469 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.112
S = 1.17
1513 reflections
239 parameters
2 restraints
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1999 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812027377/go2056sup1.cif

e-68-o2213-sup1.cif^{(20.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812027377/go2056Isup2.hkl

e-68-o2213-Isup2.hkl^{(73.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812027377/go2056Isup3.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
C4—H4⋯O2ⁱ	0.98	2.46	3.374 (5)	154
C36—H36⋯O2ⁱ	0.93	2.51	3.414 (5)	164
O8—H8⋯O5ⁱⁱ	0.82	2.22	2.969 (5)	152

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Symmetry codes: (i) Inline graphic ; (ii) .

supplementary crystallographic information

Comment

Cyclohexanone derivatives have potent pharmacological activity in the treatment of a broad spectrum of medical conditions(Puetz et al., 2003). Cyclohexanone derivatives penetrate into the stratum corneum and alter the skin permeability of indomethacin by fluidizing or modifying the hard hydrophobic barrier of the corneum(Danyi et al., 1989), thus giving an alternative method of administration of this compound which can cause serious gastric upsets.

In C₁₇H₁₉NO₈, (I), (Fig. 1), the cyclohexanone ring adopts a chair conformation [Q=0.589 (4) Å, θ=173.0 (4)° and φ=16 (3)° (Cremer & Pople, 1975)]. The mean value [56.55 (16)°] of the endocyclic torsion angles of the cyclohexanone ring in (I) shows that it is slightly more puckered than the idealized cyclohexanone ring [54.1 (3)°, MM2 calculation; (Allinger, 1977)]. The two methoxycarbonyl groups at C2 (C4—C3—C2—C21=-178.4 (2)°) and at C4 (C2—C3—C4—C41=-179.2 (3)°) are substituted in β-equatorial positions. The nitrophenyl ring(ring A) attached to C3 adopts an α equatorial orientation. The methyl and hydroxyl groups at C5 are oriented in β axial and equatorial positions respectively. The mean planes through C1, C3, C4 and C6 and ring A make a dihedral angle of 82.06 (12)°. This value is greater than that reported for a similar structure (73.76°) (Hema et al., 2006). The dihedral angle between ring A and the carboxy groups O2–C21–O3 and O6–C41–O4 are 61.14 (24)° and 74.71 (27)°, respectively. These two carbonyl groups in (I) are twisted in opposite direction with C5–C4–C41–O7 and C1–C2–C21–O2 torsion angles of 75.8 (5)° and -73.0 (4)°, respectively.

The hydroxyl group forms a strong intermolecular hydrogen bond, O8–H8···O5(-0.5+x,0.5+y,z) linking the molecules into C(10) chains, (Bernstein et al., 1995), Table 1 and Figure 2. The weak hydrogen bonds C4-H2···O2(x,-1+y,z) and C36-H36···O2(x,-1+y,z) link these chains into sheets which lie parallel to theab-plane.

Experimental

A mixture of methyl acetoacetate(11.6 g, 100 mmol), 3-nitrobenzaldehyde(7.55 g, 50 mmol) and methylamine(1.55 g, 50 mmol) in ethanol(50 ml) was heated to boiling. The reaction mixture was allowed to stand overnight. The separated solid was filtered and purified by recrystallization from ethanol to yield the title compound (yield 11.2 g, 75%, mp 475K).