Crystal structure of (2S,4R)-ethyl 4-nitro­methyl-1-[(S)-1-phenyl­eth­yl]-6-sulfanyl­idene­piperidine-2-carboxyl­ate

Araceli Zárate; David Aparicio; Angel Palillero; Angel Mendoza

doi:10.1107/S2056989014026711

. 2015 Jan 1;71(Pt 1):o41–o42. doi: 10.1107/S2056989014026711

Crystal structure of (2S,4R)-ethyl 4-nitromethyl-1-[(S)-1-phenylethyl]-6-sulfanylidenepiperidine-2-carboxylate

Araceli Zárate ^a, David Aparicio ^a, Angel Palillero ^a, Angel Mendoza ^a,^*

PMCID: PMC4331902 PMID: 25705497

Abstract

In the title compound, C₁₇H₂₂N₂O₄S, a thiopiperidine derivative, the piperidine ring has an envelope conformation with the methylene C atom opposite to the C=S bond as the flap. The nitromethyl substituent is equatorial while the ethoxycarbonyl group is axial. The mean planes of the nitromethyl group, the carboxy group and phenyl ring are inclined to the mean plane through the five planar atoms of the piperidine ring [maximum deviation = 0.070 (4) Å] by 56.8 (2), 83.8 (5) and 87.1 (2)°, respectively. There is an intramolecular C—H⋯O hydrogen bond involving an H atom of the ethoxycarbonyl group and a nitro O atom. In the crystal, molecules are linked by C—H⋯O hydrogen bonds, forming chains along [100]. The chains are linked by further C—H⋯O hydrogen bonds, forming corrugated layers lying parallel to (001).

Keywords: crystal structure, thiopiperidine, piperidine-2-thiones, hydrogen bonding

Related literature

For general background on piperidines and their derivatives, see: Poupart et al. (1999 ▸); Pinnick et al. (1990 ▸); Mukaiyama & Hoshino (1960 ▸); Ballini et al. (2007 ▸); Sośnicki (2009 ▸). For their biological activity, see: Leung et al. (2000 ▸). For their use in organometallic reactions, see: Tamaru et al. (1978 ▸, 1979 ▸). For details of the Cambridge Structural Database, see: Groom & Allen (2014 ▸). graphic file with name e-71-00o41-scheme1.jpg

Experimental

Crystal data

C₁₇H₂₂N₂O₄S
M _r = 350.42
Orthorhombic,
a = 5.7999 (2) Å
b = 10.0103 (6) Å
c = 30.4050 (18) Å
V = 1765.28 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 293 K
0.20 × 0.09 × 0.05 mm

Data collection

Agilent Xcalibur Atlas Gemini diffractometer
Absorption correction: analytical (CrysAlis PRO; Agilent, 2014 ▸) T _min = 0.979, T _max = 0.991
8486 measured reflections
3373 independent reflections
2306 reflections with I > 2σ(I)
R _int = 0.054

Refinement

R[F ² > 2σ(F ²)] = 0.056
wR(F ²) = 0.104
S = 1.04
3373 reflections
219 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.18 e Å⁻³
Absolute structure: Flack x determined using 705 quotients [(I ⁺)−(I ⁻)]/[(I ⁺)+(I ⁻)] (Parsons et al., 2013 ▸)
Absolute structure parameter: 0.16 (8)

Data collection: CrysAlis PRO (Agilent, 2014 ▸); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS2014 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2008 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸) and Mercury (Macrae et al., 2008 ▸); software used to prepare material for publication: WinGX (Farrugia, 2012 ▸), PLATON (Spek, 2009 ▸) and publCIF (Westrip, 2010 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989014026711/su5036sup1.cif

e-71-00o41-sup1.cif^{(25.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989014026711/su5036Isup2.hkl

e-71-00o41-Isup2.hkl^{(185.2KB, hkl)}

Click here for additional data file.^{(1.2MB, tif)}

. DOI: 10.1107/S2056989014026711/su5036fig1.tif

A view of the molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 30% probability level.

Click here for additional data file.^{(2MB, tif)}

a . DOI: 10.1107/S2056989014026711/su5036fig2.tif

A view along the a axis of the crystal packing of the title compound. Hydrogen bonds are shown as dashed lines (see Table 1 for details; H atoms not involved in the intermolecular hydrogen bonding have been omitted for clarity).

CCDC reference: 1037775

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

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
C16H16AO3	0.96	2.49	3.419(8)	163
C2H2AO1ⁱ	0.97	2.55	3.404(5)	147
C17H17BO3ⁱⁱ	0.97	2.58	3.380(6)	140

Open in a new tab

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

Acknowledgments

We are grateful to CONACyT (project 154104) for financial support and AZ thanks CONACyT for a postdoctoral scholarship (165517).

supplementary crystallographic information

S1. Comment

The Michael addition is one of the most important synthetic strategies performed in organic synthesis. Among the many applications, conjugate addition to α,β-unsaturated δ-lactams has been used in the synthesis of functionalized piperidines, due to a wide range of biological activities (Leung et al., 2000). Similar to α,β-unsaturated δ-lactams, α,β-unsaturated δ-thiolactams are promising Michael acceptors affording 4-substituted piperidine-2-thiones (Sośnicki, 2009). They also form C—C bonds in the reaction with organometallics such as alkyllithium, alkylmagnesium (Tamaru et al., 1978) and lithium enolates (Tamaru et al., 1979). Among a broad range of nucleophiles applied to the C—C bond formation, the addition of aliphatic nitrocompounds play a significant role (Ballini et al., 2007). In the presence of a base catalyst, the introduction of a nitroalkyl group into a α,β-unsaturated compound represent a key step in the preparation of chiral molecules due to versatile reactivity of the nitro functionality. The corresponding nitro compounds can be transformed into a wide range of synthetically valuable products such as amines (Poupart et al., 1999), ketones (Pinnick et al., 1990), carboxylic acids, nitrile oxides and other functionalities (Mukaiyama et al., 1960).

In the title compound, Fig. 1, the piperidine ring has an envelope conformation with puckering parameters Q = 0.528 (4) Å, θ = 129.0 (4)°, φ = 314.6 (6)°, q₂ = 0.411 (4)° and q₃ = -0.332 (4)°. The phenyl-ethyl group linked atom N1 of the piperidine ring, shows a dihedral angle of 101.6 (4)° from the mean plane of the piperidine ring. The carboxyethyl group is placed in a axial position (torsion angle = 15.8 (3)°) and the nitromethyl group in an equatorial position (torsion angle = 73.7 (3)°) on the piperidine ring. The C5═S1 distance is 1.682 (4) Å, similar to that found for other piperidine-2-thiones (CSD; Groom & Allen, 2014). There is an intramolecular C-H···O hydrogen bond present (Table 1).

In the crystal, molecules are linked by C-H···O hydrogen bonds forming chains along [100], which are linked by further C-H···O hydrogen bonds forming corrugated layers lying parallel to (001); see Table 1 and Fig. 2.

S2. Experimental

α,β-Unsaturated piperidine-2-thione derived from (S)-(-)-phenylethylamine (1.0 mmol) was dissolved in a solution of nitroalkane, and a catalytic amount of DBU was added. The mixture was stirred at room temperature for 2 h. When the reaction was complete, 5 ml of concentrated NH₄Cl was added and the solution was extracted twice with ethyl acetate. The organic phase was dried, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica (petroleum ether/ethyl acetate 80:20) giving the title compound as a white solid (yield 80%; m.p. 383- 385 K). It was crystallized using petroleum ether/dichloromethane, giving colourless prismatic crystals. [α]D²⁰= -92.3 (c 1.0, CH₂Cl₂). IR (KBr pellet, cm^-1): ν= 3746, 2977, 2929, 1739, 1551, 1461, 1196, 1075, 701, 548. ¹H NMR (500 MHz, CDCl₃): δ 1.31 (t, J = 7.1 Hz, 3H), 1.33 (m, 1H), 1.52 (d, J = 7.1 Hz, 3H), 2.25 (ddd, J = 1.9, 5.7, 13.7 Hz, 1H), 2.79 (m, 1H), 2.99 (dd, J = 7.2, 18.3 Hz, 1H), 3.37 (ddd, J = 0.6, 7.7, 18.3 Hz, 1H), 4.05 (dd, J = 2.4, 5.4 Hz, 1H), 4.21 (dd, J = 8.4, 12.8 Hz, 1H), 4.27 (m, 2H), 4.35 (dd, J = 6.1, 12.8 Hz, 1H), 7.35 (m, 5H). ¹³C NMR (100 MHz, CDCl₃) δ 14.1, 14.5, 28.5, 29.9, 43.4, 55.6, 58.4, 62.5, 78.8, 127.0–129.0, 138.2, 170.0, 199.1.