Crystal and molecular structure of (S)-N-(2-hydroxyphenyl)pyrrolidine-2- carboxamide

Article abstract of DOI:10.1007/s10870-010-9935-z

(S)-N-(2-Hydroxyphenyl)pyrrolidine-2-carboxamide was synthesized from Cbz-l-proline through two steps and characterized by NMR and MS. The crystal structure was determined from single-crystal X-ray diffraction data. It crystallizes in the monoclinic space group, P2₁, with unit cell dimensions a = 7.284(6) A, b = 10.262(9) A, and c = 7.975(7) A, α = 90.00°, β = 114.451(14)°, γ = 90.00° and Z = 2. The absolute configuration of the chiral center is determined as S. In the crystal structure, intermolecular and intramolecular hydrogen bonds are responsible for the formation of a 1-dimensional network.

Full text of DOI:10.1007/s10870-010-9935-z

J Chem Crystallogr (2011) 41:251–254
DOI 10.1007/s10870-010-9935-z
NOTE
Crystal and Molecular Structure of (S)-N-
(2-Hydroxyphenyl)pyrrolidine-2-carboxamide
•
Gang Chen Ying Tang Qun-Zheng Zhang
•
•
•
Mei Meng Xiao-Jiang Hao
Received: 2 March 2010 / Accepted: 10 December 2010 / Published online: 25 December 2010
Ó Springer Science+Business Media, LLC 2010
Abstract (S)-N-(2-Hydroxyphenyl)pyrrolidine-2-carbox-
amide was synthesized from Cbz-L-proline through two
steps and characterized by NMR and MS. The crystal
structure was determined from single-crystal X-ray dif-
fraction data. It crystallizes in the monoclinic space group,
hydrogen bond, which ensures that the reaction proceeds
on only one face of the pyrrolidine ring; it lowers the
activation barrier of the reaction by charge stabilization
along the C–C bond formation by means of the intramo-
lecular hydrogen bond [1–5]. Based on this mechanism,
many proline derivatives have been designed, synthesized
and used in the asymmetric aldol condensations [6–8]. The
tile compound, (S)-N-(2-hydroxyphenyl)pyrrolidine-2-car-
boxamide, has been synthesized and used in the cataly-
sis synthesis of asymmetric Aldol condensation and
Michael addition [9, 10]. In this article, we synthesized
(S)-N-(2-hydroxyphenyl)pyrrolidine-2-carboxamide (shown
as Scheme 1) and determined the crystal structure by
single-crystal X-ray diffraction.
˚
P21, with unit cell dimensions a = 7.284(6) A, b = 10.26
˚
˚
2(9) A, and c = 7.975(7) A, a = 90.00°, b = 114.45
1(14)°, c = 90.00° and Z = 2. The absolute configuration
of the chiral center is determined as S. In the crystal
structure, intermolecular and intramolecular hydrogen
bonds are responsible for the formation of a 1-dimensional
network.
Keywords L-Proline Á (S)-N-(2-Hydroxyphenyl)
pyrrolidine-2-carboxamide Á X-ray structure
Experimental
Introduction
All starting materials and solvents (A.R. grade) were
commercially available and were used without further
purification. NMR spectra were recorded in the stated
solutions, on a Bruker Drx-400 spectrometer, operating at
500 MHz for 1H and 125 MHz for 13C; d values are
reported in ppm and J values in hertz. Mass spectra were
recorded on a Micromass Platform II spectrometer, using
the direct-inlet system operating in the electron impact
(ESI) mode at 75 eV.
Proline, as well as its derivatives, has been widely used in
asymmetric aldol condensation and related reactions as a
bifunctional catalyst since it was first used by List [1–3].
Several theoretical studies have highlighted the importance
of the carboxylic acid functionality of proline in this
reaction: it orients the incoming aldehyde through a
G. Chen (&) Á Y. Tang Á Q.-Z. Zhang Á M. Meng
College of Chemistry and Chemical Engineering, Xi’an Shiyou
University, Xi’an 710065, Shaanxi, People’s Republic of China
e-mail: gangchen@xsyu.edu.cn
Synthesis of (S)-N-(2-Hydroxyphenyl)pyrrolidine-2-
carboxamide
X.-J. Hao
0.249 g Cbz-L-proline (1 mmol), 0.019 g o-aminophenol,
and 0.206 g DCC and 0.012 g DMAP was dissolved in
15 mL anhydrous THF. The mixture was stirred under
room temperature. Completion of the reaction was
State Key Laboratory of Phytochemistry and Plant Resources
in West China, Kunming Institute of Botany, Chinese Academy
of Sciences, Kunming 650204, Yunnan, People’s Republic of
China
123

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J Chem Crystallogr (2011) 41:251–254
Scheme 1 Synthesis of (S)-N-
(2-hydroxyphenyl)pyrrolidine-
2-carboxamide
O
O
O
H2N
HO
H2
DCC
N
N
HN
HN
+
N
OH
H
Pd/C
DMAP
Cbz
Cbz
HO
HO
monitored by TLC check, the solvent was distilled off
under reduced pressure and the residue was separated by
column chromatography (silica gel, petroleum ether/ethyl
acetate = 10:1–4:1) to give the target products. Colorless
crystals of the title compound were obtained in ethanol by
recrystallization. Overall yield 67%; m.p. 170–172 °C
1.73 (1H, m), 1.43 (1H, m), 1.30 (1H, m); 13C-NMR
(D6-Acetone, 125 MHz), d: 206.2, 176.3, 155.4, 131.4,
129.8, 125.0, 120.5, 117.9, 64.0, 49.1, 26.5, 25.9; MS (ESI)
m/z: 207 (M ? 1).
X-ray Data Collection and Structure Refinement
(170 °C [10]); [a]2D0 = -47.0 (c = 1.0, CH3OH) ([a]2D0
=
1
-45.6 (c = 1.0, CH2Cl2H) [10]); H-NMR (D6-Acetone,
500 MHz), d: 7.16 (1H, d, J = 1.0 Hz), 7.05 (1H, dd,
J = 8.0, 1.5 Hz), 6.94 (1H, dd, J = 8.0, 1.0 Hz), 6.85 (1H,
d, J = 1.5 Hz), 3.98 (1H, dd, J = 9.5, 4.5 Hz), 2.95 (1H,
m), 2.82 (1H, m), 2.08 (1H, m), 1.96 (1H, m), 1.84 (1H, m),
All H atoms were positioned geometrically, with C–H
˚
= 0.93–0.98 A, and refined with a riding model, with
˚
Table 2 Selected bond lengths (A) and angles (°)
˚
Dist. (A)
˚
Dist. (A)
Bond
Bond
C6–C7
C6–C11
C6–N2
C10–C9
C10–C11
O1–C5
N2–C5
O2–C7
1.398(3)
1.386(3)
1.409(3)
1.388(4)
1.390(4)
1.239(3)
1.333(3)
1.355(3)
C8–C9
C8–C7
C1–N1
C1–C5
C1–C2
N1–C4
C3–C2
C3–C4
1.370(4)
1.394(3)
1.465(3)
1.513(3)
1.545(4)
1.459(4)
1.513(5)
1.527(5)
Table 1 Experimental data
Empirical formula
Formula weight
Temperature
C11H14N2O2
206.24
296(2)
Wavelength (Mo Ka)
Crystal system
Space group
0.71073
Monoclinic
P21
Crystal data
´
˚
Angle
(°)
Angle
(°)
a (A)
7.284(6)
´
˚
b (A)
10.262(9)
C7–C6–C11
C7–C6–N2
C11–C6–N2
C5–N2–C6
C9–C8–C7
C10–C11–C6
N1–C1–C5
N1–C1–C2
C5–C1–C2
C1–N1–C4
119.4(2)
O1–C5–C1
N2–C5–C1
C8–C9–C10
O2–C7–C6
O2–C7–C8
C6–C7–C8
C3–C2–C1
N1–C4–C3
O1–C5–N2
C2–C3–C4
121.19(19)
115.35(18)
120.6(2)
´
˚
c (A)
7.975(7)
116.11(18)
124.46(19)
127.83(18)
120.3(2)
a (°)
b (°)
c (°)
Volume
90.00
114.451(14)
116.43(19)
123.93(19)
119.6(2)
90.00
542.7(8)
120.5(2)
Z
2
112.32(18)
106.4(2)
104.5(2)
Density (calculated)
Absorption coefficient
F(000)
1.263 mg/m3
106.0(2)
0.123
111.2(2)
123.5(2)
242
0.47 9 0.40 9 0.28 mm3
108.2(2)
101.9(2)
Crystal size
Theta range for data collection (°) 1.5–25.0
Index ranges
-9 B h B 6; -13 B k B 13;
-9 B l B 10
3376
Reflections collected
Independent reflections
Reflections theta (°)
2402
2.8–28.3
Absorption correction transmission 0.7661–0.8346
Refinement method
Full-matrix least-squares on F2
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2r(I)]
R indices (all data)
2402/1/137
1.099
R1 = 0.0574; wR2 = 0.1499
R1 = 0.0514; wR2 = 0.1570
-0.261 to 0.045
Refine different density
Fig. 1 The molecular structure of the title molecule
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J Chem Crystallogr (2011) 41:251–254
253
Fig. 2 The intermolecular
hydrogen bonds in the crystal
U
iso(H) = 1.2 Ueq(carrier). Data collection: SMART [11];
and eliminating conformational flexibility. Intermolecu-
lar hydrogen bonds of the type O–HÁÁÁO are found in
the crystal structure, O(2)–H(2B)ÁÁÁO(1) [O(2)ÁÁÁO(1) =
cell refinement: SAINT [11]; data reduction: SAINT [11];
program (s) used to solve structure: SHELXS97 [12];
program (s) used to refine structure: SHELXL97 [13];
molecular graphics: Ortep-3 for Windows [14]; software
used to prepare material for publication: WinGX [15].
˚
2.643(3) A, \O(2)H(2B)O(1) = 174° (Fig. 2), and gener-
ate 1-D supra-molecular structures. In the crystal, the
phenyl moieties pack together layer by layer staggeredly,
˚
the distance of the planes is 5.884(5) A, and no p–p
stacking interactions are observed.
Results and Discussion
Supplementary Material
The main experimental data is displayed in Table 1;
selected bond lengths and bond angles for the title com-
pound are listed in Table 2. The molecular structure is
shown in Fig. 1, and the intermolecular hydrogen bonds are
depicted in Fig. 2. The X-ray structural determination of
the title compound confirmed the assignment of its struc-
ture from NMR and MS spectra data.
Crystallographic data for the structure reported in this
paper have been deposited at the Cambridge Crystallo-
graphic Data Center. Copies of the data (CCDC 768004)
can be obtained free of charge upon application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK (E-mail:
deposit@ccdc.cam.ac.uk).
Geometric parameters of the title compound are in the
usual ranges. It crystallizes in the monoclinic space group,
˚
P21, with unit cell dimensions a = 7.284(6) A, b = 10.
Acknowledgments This work was financially supported by the
grants from Scientific Research Plan Projects of Natural Science
Research Plan Projects of Shaanxi Science and Technology Depart-
ment (SJ08B20) and Scientific Research Plan Projects of Shaanxi
Education Department (09JK702).
˚
˚
262(9) A, and c = 7.975(7) A. In the molecule, there are
two rings, pyrrolidine and phenyl connected by a carbox-
amide group. The pyrrolidine displays a typical envelope
conformation, C1, C2, C4 and N1 compose a plane with the
C2–C1–N1–C4 torsion angle of -4.007(275)°, and C3
projects out of this plane, C2–C3 and C4–C3 formed the
flap of the envelope. The bond angles of the pyrrolidine
part are in the range of 101.929(296)° (C2–C3–C4) to
108.146(213)° (C4–N1–C1). The absolute configuration
could not be determined by anomalous dispersion effects,
but was assigned with reference to an unchanging chiral
center in the parent molecule. The plane of the carbox-
amide group contents the atoms of C1, C5, O1 and N2 with
the dihedral angle of 23.719(184)° between phenyl plane.
N2, C6, C7 and O2 compose a plane with the N2–C6–C7–
O2 torsion angle of -1.066(308)°.
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There are intramolecular hydrogen bonds in the title
˚
molecule: N(2)–H(2A)ÁÁÁO(2) [N(2)ÁÁÁO(2) = 2.622(3) A,
\N(2)H(2A)O(2) = 103°] and N(2)–H(2A)ÁÁÁN(1) [N(2)ÁÁÁ
˚
N(1) = 2.622(3) A, \N(2)H(2A)N(1) = 114°] (Fig. 1).
The intramolecular hydrogen bonds form two pseudo-five-
membered rings, thus locking the molecular conformation
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J Chem Crystallogr (2011) 41:251–254
¨
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