Ethyl 2,6-bis­(4-bromo­phen­yl)-1-iso­cyano-4-oxo­cyclo­hexa­necarboxyl­ate

Dawei Zhang; Linlin Hao; Jing Li

doi:10.1107/S160053681401530X

. 2014 Jul 5;70(Pt 8):o856. doi: 10.1107/S160053681401530X

Ethyl 2,6-bis(4-bromophenyl)-1-isocyano-4-oxocyclohexanecarboxylate

Dawei Zhang ^a, Linlin Hao ^a, Jing Li ^b,^*

PMCID: PMC4158533 PMID: 25249907

Abstract

In the title compound, C₂₂H₁₉Br₂NO₃, the central oxocyclohexane ring is in a twist-boat conformation; all the substituents (one ethoxycarbonyl and two aryl groups) are located in equatorial orientations. One of the –CH₂– groups and the opposite –CH– group bearing a bromobenzene substituent form the flagpoles of the twist-boat. The dihedral angle between the aromatic rings is 76.4 (4)°. In the crystal, weak C—H⋯O interactions link the molecules into C(5) chains propagating in the [010] direction. A short Br⋯O contact of 3.254 (4) Å is observed.

Keywords: crystal structure

Related literature

For further details of the synthesis, see: Tan et al. (2009 ▶); Zhang et al. (2010 ▶). For more [5 + 1] annulation reactions, see: Bi et al. (2005 ▶); Dong et al. (2005 ▶); Hu et al. (2008 ▶); Zhao et al. (2006 ▶); Fu et al. (2009 ▶); Xu et al. (2012 ▶).

Experimental

Crystal data

C₂₂H₁₉Br₂NO₃
M _r = 505.20
Monoclinic,
a = 21.9920 (17) Å
b = 11.0750 (19) Å
c = 17.648 (3) Å
β = 103.560 (2)°
V = 4178.6 (11) Å³
Z = 8
Mo Kα radiation
μ = 3.90 mm⁻¹
T = 293 K
0.17 × 0.16 × 0.13 mm

Data collection

Bruker SMART APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2007 ▶) T _min = 0.557, T _max = 0.631
10763 measured reflections
3904 independent reflections
2578 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.043
wR(F ²) = 0.113
S = 1.03
3904 reflections
253 parameters
H-atom parameters constrained
Δρ_max = 1.11 e Å⁻³
Δρ_min = −0.92 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) I. DOI: 10.1107/S160053681401530X/hb7238sup1.cif

e-70-0o856-sup1.cif^{(21KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681401530X/hb7238Isup2.hkl

e-70-0o856-Isup2.hkl^{(191.5KB, hkl)}

Click here for additional data file.^{(7.1KB, cml)}

Supporting information file. DOI: 10.1107/S160053681401530X/hb7238Isup3.cml

CCDC reference: 1011009

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C11—H11⋯O3ⁱ	0.98	2.58	3.226 (5)	123

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Symmetry code: (i) Inline graphic .

Acknowledgments

Financial support of this research by the Science and Technology Development Program Foundation of Jilin Province (No. 20140204022NY), the Interdisciplinary Innovation Fund of Jilin University (No. 450060481143) and the PhD Fund of Jilin University (No. 20140402) is gratefully acknowledged

supplementary crystallographic information

S1. Introduction

S2. Experimental

S2.1. Synthesis and crystallization

To a mixture of (1E,4E)-1,5-bis(4-bromophenyl)penta-1,4-dien-3-one (392 mg, 1.0 mmol) and ethyl isocyanoacetate (0.132 mL, 1.2 mmol) in DMF (5 ml) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (0.015 mL, 0.1 mmol) in one portion at room temperature. The reaction mixture was stirred at room temperature, and the reaction mixture was monitored by TLC. After the substrate (1E, 4E)-1,5-bis(4-bromophenyl)penta-1,4-dien-3-one was consumed, the resulting mixture was poured into ice-water (30 ml) under stirring. The precipitated solid was collected by filtration, washed with water (3 × 10 ml), and dried under vacuum to afford the crude product which was purified by flash chromatography (silica gel, petroleum ether : diethyl ether = 3:1, v/v) to give the title compound (460 mg, 91%). The material was recrystallized from a mixture of petroleum ether and diethyl ether to provide colourless blocks. For further synthesis details, see: Tan et al. (2009); Zhang et al. (2010).

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1.

Hydrogen atoms were generated in idealized positions (according to the sp2 or sp3 geometries of their parent carbon), and then refined using a riding model with fixed C—H distances (C—H = 0.95–1.00 Å) and with Uiso(H) = 1.2Ueq(C).

S3. Results and discussion

Comment

In the process of strategies developing of [5+1] annulation for the construction of six-membered cyclic compounds, we have found that ethyl isocyanoacetate is an active carbon nucleophile that can react with divinyl ketone through a tandem double Michael-addition cyclization. This one-step annulation can regiospecificly forms highly constrained cyclohexane analogues of phenylanaline (Phe) which are precursors for the synthesis of peptide analogues with controlled fold in the backbone. The constrained ring systems play important roles in restricting torsional angle χ1 and in peptide receptor recognition processes, thus the [5+1] annulation reactions have drew much attentions and both the five-carbon 1,5-bielectrophiles and the one-atom nucleophiles been explored extensively (Bi et al., 2005; Dong et al., 2005; Hu et al., 2008; Zhao et al., 2006; Fu et al., 2009; Xu et al., 2012).

The title compound, a phenyl substituted highly constrained cyclohexane analogue of Phe, is one of the products obtained during the study of [5+1] annulation of divinyl ketone and isocyanoacetate. In the crystal, the central six-member oxocyclohexane ring adopts a twist-boat conformation (Fig. 1), and all of the ethoxyl carbonyl and two aryl groups are located in equatorial positions. The aryl groups are trans to each other and the dihedral angle between two aromatic rings is 76.45 (4) °. In this molecular, C11 with axial hydrogen and C8 (CH₂) are on the flagpole positions of the boat conformation, which give the least torsional strain. C12 and C7 are on one side of the boat conformation, and their equatorial substituents, ethoxyl carbonyl and aryl groups, fit in with the formation boat conformation of this compound.