N-But­oxy­carbonyl-5-oxo-l-proline ethyl ester

P Rajalakshmi; N Srinivasan; RV Krishnakumar; Ibrahim Abdul Razak; Mohd Mustaqim Rosli

doi:10.1107/S1600536813007265

. 2013 Mar 23;69(Pt 4):o567–o568. doi: 10.1107/S1600536813007265

N-Butoxycarbonyl-5-oxo-l-proline ethyl ester

P Rajalakshmi ^a, N Srinivasan ^a,^*, RV Krishnakumar ^a, Ibrahim Abdul Razak ^b, Mohd Mustaqim Rosli ^b

PMCID: PMC3629616 PMID: 23634103

Abstract

The molecular structure of the title compound, C₁₂H₁₉NO₅, may be visualized as made up of two nearly perpendicular planes [dihedral angle = 87.39 (12)°] and its crystal structure is a good example of C—H⋯O interactions assuming significance in optimizing supramolecular aggregation in crystals in a molecule which is severely imbalanced in terms of donors to acceptor atoms. The pyrrolidine ring adopts a (³ T ₂) twist conformation with puckering parameters Q = 0.2630 (4) Å and ϕ = 59 (9)°. The crystal structure features R ₂ ⁴(10) and R ₃ ⁴(26) ring motifs formed by four weak C—H⋯O interactions, leading to supramolecular sheets lying parallel to the bc plane.

Related literature

For general background, see: Holladay et al. (1991 ▶); Kayushina & Vainshtein (1966 ▶); Wu (2009 ▶). For the biological activity of proline derivatives, see: Hayashi et al. (2003 ▶); Nishikawa & Murakami (2005 ▶). For hydrogen bonding, see: Bernstein et al. (1995 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For a description of the Cambridge Structural Database, see: Allen (2002 ▶).

Experimental

Crystal data

C₁₂H₁₉NO₅
M _r = 257.28
Orthorhombic,
a = 26.6884 (13) Å
b = 5.7650 (3) Å
c = 8.7054 (4) Å
V = 1339.40 (11) Å³
Z = 4
Cu Kα radiation
μ = 0.83 mm⁻¹
T = 100 K
0.44 × 0.21 × 0.11 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.711, T _max = 0.914
9641 measured reflections
2184 independent reflections
2144 reflections with I > 2σ(I)
R _int = 0.049

Refinement

R[F ² > 2σ(F ²)] = 0.060
wR(F ²) = 0.166
S = 1.09
2184 reflections
167 parameters
H-atom parameters constrained
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.22 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

Click here for additional data file.^{(23.5KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813007265/bx2436sup1.cif

e-69-0o567-sup1.cif^{(23.5KB, cif)}

Click here for additional data file.^{(105.2KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813007265/bx2436Isup2.hkl

e-69-0o567-Isup2.hkl^{(105.2KB, hkl)}

Click here for additional data file.^{(5.3KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813007265/bx2436Isup3.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
C2—H2A⋯O3ⁱ	1.00	2.51	3.436 (5)	154
C3—H3B⋯O3ⁱⁱ	0.99	2.46	3.095 (5)	121
C6—H6B⋯O5ⁱⁱⁱ	0.99	2.50	3.344 (5)	143
C12—H12A⋯O5ⁱ	0.98	2.55	3.327 (5)	136

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

Acknowledgments

The authors thank Dr MutharasuDevarajan, Associate Professor, and the staff of the X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, for their help with the data collection.

supplementary crystallographic information

Comment

Proline (Kayushina & Vainshtein, 1966) is a functional amino acid that participates in the regulation of key metabolic pathways essential for maintenance, growth, reproduction and immunity (Wu, 2009). Many substituted proline derivatives are known for their active role in biological functions. For instance, 5-oxo-proline or pyroglutamic acid, found in many proteins including bacteriorhodopsin, acts as a proton pump, captures light energy and uses it to move protons across the membrane out of the cell (Hayashi, et al., 2003; Nishikawa, et al., 2005). Also, N-boc-4-oxo-L-proline ethyl ester is a part of the starting material on stereoselective synthesis of peptide hormone cholecystokinin (Holladay, et al., 1991). The present paper describes the accurate description of the crystal structures of N-boc-5-oxo-L-proline ethyl ester (Fig.1).

The molecular mainframe of the title compound may be visualized as made up of two nearly perpendicular planes (N1/C8/O4/O5) and (O1/C1/O2/C2) with 87.39 (12) °. The orientation of the carbonyl O3 (substituted to the pyrrolidine ring), O4 (ethyl ester carbonyl) and O5 (tert-butyloxycarbonyl) may be described by the torsion angles about the C2—N1 bond which are -171.05 (4) °, -54.37 (6) ° and -170.82 (4) °, respectively. The pyrrolidine adopts the twisted conformation (³T₂) with C2 and C3 atoms deviating from the plane defined by the rest of the atoms by about -0.3872 (6) Å and 0.4068 (6) Å, respectively with the associated puckering parameters (Cremer & Pople, 1975) of Q=0.2630 (4) Å, φ= 59 (9) °.

The crystal structure of the title compound is a simple example which demonstrates the importance of weak C–H···O interactions assuming significance in optimizing supramolecular aggregation in crystals. The molecule may be thought of as highly imbalanced in terms of donors to acceptor atoms which has at least three carbonyl O atoms O3, O4 and O5, out of the total five O atoms (O1→O5), available for participation in intermolecular interactions. O1 and O2 of the respective ethyl ester and the tert-butyloxy groups do not participate in the hydrogen-bonding environment owing to unfavourable steric reasons. The intermolecular interaction patterns may be vizualized as molecular chains interconnected to each other to form a sheet. The ethyl C2 and ethyl C3 atoms act as donors to the carbonyl O3 which is a bifurcated acceptor at (x, y - 1, z) and (-x + 2, y - 1/2, -z + 1/2), respectively. The associated graph-set motif (Bernstein et al., 1995) is a R⁴₂(10) ring through C2—H2A···O3 and C3—H3A···O3 hydrogen bond leading to chains parallel to the b-axis (Fig.2). The ethyl C6 and ethyl C12 atoms act as donors to the bifurcated acceptor (carbonyl) O5 at (x, y, z + 1) and (x, y - 1, z), respectively, forming a R⁴₃ (26) ring motif through a C6—H6B···O5 and C12—H12A···O5 hydrogen bonds forming sheets parallel to the bc-plane (Fig.3).

Experimental

To a solution of oxo proline ethylester (0.5 g,3.26 mmol) in dichloromethane (10 ml), was added triethylamine (0.5 ml, 3.26 mmol), di-tert-butyl-dicarbonate (1.4 g, 6.52 mmol) and 4-(dimethylamino)-pyridine (0.4 g, 3.26 mmol) under N2. The resulting yellow solution was stirred at room temperature for 2 h. The reaction mixture was concentrated. The residue was purified by column chromatography to afford boc-oxo-L-proline ethylester (0.8 g, 95%). Crystals of the title compound were grown from its solution in ethanol by slow evaporation at room temperature.