2-Hydr­oxy-16-[(E)-4-hydr­oxy-3-methoxy­benzyl­idene]-13-(4-hydr­oxy-3-methoxy­phen­yl)-11-methyl-1,11-diaza­penta­cyclo­[12.3.1.02,10.03,8.010,14]octa­deca-3(8),4,6-triene-9,15-dione

Raju Suresh Kumar; Hasnah Osman; Mohamed Ashraf Ali; Madhukar Hemamalini; Hoong-Kun Fun

doi:10.1107/S1600536810017216

. 2010 May 15;66(Pt 6):o1370–o1371. doi: 10.1107/S1600536810017216

2-Hydroxy-16-[(E)-4-hydroxy-3-methoxybenzylidene]-13-(4-hydroxy-3-methoxyphenyl)-11-methyl-1,11-diazapentacyclo[12.3.1.0^2,10.0^3,8.0^10,14]octadeca-3(8),4,6-triene-9,15-dione

Raju Suresh Kumar ^a, Hasnah Osman ^a,^‡, Mohamed Ashraf Ali ^b, Madhukar Hemamalini ^c, Hoong-Kun Fun ^c,^*,^§

PMCID: PMC2979481 PMID: 21579453

Abstract

In the title compound, C₃₂H₃₀N₂O₇, the piperidone ring adopts a chair conformation and the five-membered ring of the dihydroindenone ring system adopts an envelope conformation. Intramolecular O—H⋯N and C—H⋯O hydrogen bonds occur. The dihedral angle between the two hydroxy-subsituted methoxyphenyl rings is 71.12 (5)°. In the crystal structure, molecules are connected by intermolecular O—H⋯O hydrogen bonds, forming layers parallel to (001). These layers are further connected by C—H⋯O hydrogen bonds, forming a three-dimensional network.

Related literature

For details of 1,3-dipolar cycloaddition, see: Padwa (1984 ▶). For applications of pyrrolidines, see: Dalko & Moisan (2004 ▶); Seayad & List (2005 ▶); Natarajan et al. (2006 ▶); O’Hagan (2000 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₃₂H₃₀N₂O₇
M _r = 554.58
Orthorhombic,
a = 14.7989 (11) Å
b = 15.4918 (11) Å
c = 22.9079 (17) Å
V = 5251.9 (7) Å³
Z = 8
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.39 × 0.39 × 0.31 mm

Data collection

Bruker APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.962, T _max = 0.969
130228 measured reflections
9672 independent reflections
7897 reflections with I > 2σ(I)
R _int = 0.048

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 0.145
S = 1.09
9672 reflections
385 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.59 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; 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 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810017216/is2545sup1.cif

e-66-o1370-sup1.cif^{(29.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810017216/is2545Isup2.hkl

e-66-o1370-Isup2.hkl^{(463.6KB, 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
O5—H1O5⋯O2ⁱ	0.89 (2)	1.77 (2)	2.6554 (14)	173 (2)
O7—H1O7⋯O4ⁱⁱ	0.88 (3)	2.13 (3)	2.8720 (13)	143 (2)
O2—H1O2⋯N2	0.92 (3)	1.91 (2)	2.5987 (13)	131 (2)
C1—H1A⋯O7ⁱⁱⁱ	0.97	2.49	3.3771 (16)	151
C13—H13A⋯O7^iv	0.93	2.57	3.3237 (17)	138
C27—H27A⋯O1	0.93	2.52	3.0998 (15)	121
C32—H32A⋯O3^v	0.96	2.40	3.1819 (17)	139

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

The synthetic chemistry work was funded by Universiti Sains Malaysia (USM) under the University Research grant No. 1001/PKIMIA/8111016. HKF and MH thank the Malaysian Government and Universiti Sains Malaysia for the Research University Golden Goose grant No. 1001/PFIZIK/811012. RSK and MH also thank Universiti Sains Malaysia for post-doctoral research fellowships.

supplementary crystallographic information

Comment

1,3-Dipolar cycloadditions represent one of the most versatile tools for the construction of five-membered heterocycles (Padwa, 1984). A diverse array of biologically active molecules contain substituted pyrrolidine cores (O'Hagan, 2000). Pyrrolidines are important building blocks in organic synthesis, and in the past years have emerged as privileged organocatalysts (Dalko & Moisan, 2004; Seayad & List, 2005). Compounds containing the piperidine subunit act as excellent inhibitors of p38 activity and TNF–α release (Natarajan et al., 2006) and consequently, the efficient preparation of these heterocycles has received significant attention.

The molecular structure of the title compound is shown in Fig. 1. The piperidone (N1/C1–C5) ring adopts a chair conformation [Q = 0.6146 (12) Å, Θ = 145.39 (11)°, φ = 120.0 (2)° ; Cremer & Pople, 1975]. The pyrrolidine ring (N2/C4/C6–C8) adopts an envelope conformation [puckering parameters Q = 0.3365 (12) Å, φ = 84.3 (2)°]. The five membered ring of the ninhydrin system adopts an envelope conformation and its flap atom C8 deviates from the mean plane formed by other atoms, C9–C16, by 0.0702 (12) Å. The dihedral angle between the two hydroxy subsituted methoxyphenyl rings (C18–C23 and C26–C31) is 71.12 (5)°.

In the crystal packing (Fig. 2), molecules are connected by intermolecular O2—H1O5···O2, O7—H1O7···O4, C1—H1A···O7, C13—H13A···O7 and C32—H32A···O3 hydrogen bonds to form a three–dimensional network.

Experimental

A mixture of 3,5-bis[(E)–(4-hydroxy-3-methoxyphenyl)methylidene] tetrahydro–4(1H)–pyridinone (0.100 g, 0.272 mmol), ninhydrin (0.049 g, 0.272 mmol), and sarcosine (0.024 g, 0.272 mmol) were dissolved in methanol (10 mL) and refluxed for 1 hour. After completion of the reaction as evident from TLC, the mixture was poured into water (50 mL). The precipitated solid was filtered and washed with water to afford the product which was recrystallized from petrolium ether-ethyl acetate mixture (1:1) to reveal the title compound as yellow crystals.