The ring-opening of chiral oxazoline involving pyrrolidone

Article abstract of DOI:10.1007/s11164-012-0794-4

Chiral N-[1-benzyl-2-hydroxyethyl]-3-[2-oxo-pyrrole]propionamide (C ₁₆H₂₂N₂O₃) was obtained unexpectedly from the reaction of oxazoline involving pyrrolidone with copper acetate monohydrate, and the structure wa

Full text of DOI:10.1007/s11164-012-0794-4

Res Chem Intermed (2013) 39:2735–2739
DOI 10.1007/s11164-012-0794-4
The ring-opening of chiral oxazoline involving
pyrrolidone
•
Luo Mei Zhang Jia Hai Yin Hao
•
Received: 27 June 2012 / Accepted: 27 August 2012 / Published online: 8 September 2012
Ó Springer Science+Business Media B.V. 2012
Abstract Chiral
N-[1-benzyl-2-hydroxyethyl]-3-[2-oxo-pyrrole]propionamide
(C16H22N2O3) was obtained unexpectedly from the reaction of oxazoline involving
pyrrolidone with copper acetate monohydrate, and the structure was characterized
by NMR, IR, elemental analysis, and X-ray analysis.
Keywords Chiral N-[1-benzyl-2-hydroxyethyl]-3-[2-oxo-pyrrole]propionamide Á
Oxazoline involving pyrrolidone Á Copper acetate monohydrate
Introduction
Chiral hydroxy amide compounds are widely used in bio-pharmaceutical and
organic synthesis reactions. Many methods for the synthesis of hydroxy amide have
already been developed [1–3], but they are most commonly prepared by the
condensation of amino alcohols with carboxylic acids [4–6] or by the ring-opening
under Lewis acid catalysis [7]. In this paper, we report for the first time the ring-
opening of oxazoline involving pyrrolidone catalyzed by a large amount of copper
acetate monohydrate.
Results and discussion
Firstly, we adopted a one-pot, efficient method to synthesize 1-[2-[(4S)-4,5-dihydro-
4- (phenylmethyl)-2-oxazolyl]ethyl]-2-pyrrolidone (compound I), which is prepared
L. Mei (&)
Department of Chemical Engineering, Hefei University of Technology, Hefei 230009, China
e-mail: lmhh5523385@yahoo.cn; luomeihuahua@sohu.com
Z. J. Hai Á Y. Hao
University of Science and Technology of China, Hefei 230009, China
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L. Mei et al.
Cu(OAc)2 H2O
O
O
O
O
CH2Ph
O
CH2OH
N
N
N
CN
83.3mol%
N
N
H
CH2Ph
I
II
Scheme 1 The synthetic route to compound II
from the 3-(2-oxo-pyrrolidin-1-yl)-propionitrile and L-phenylglycinol in chloroben-
zene, under free-water and free-oxygen condition, ZnCl2 was dried under the
vacuum and acted as the Lewis catalyst in this reaction (Scheme 1).
Compound I is then directly reacted with copper acetate monohydrate in ethanol,
after reflux for 48 h, and recrystallized with hexane and ethanol, and colorless
crystals were obtained (Figs. 1, 2). Our target was to synthesize the N–Cu complex,
but, unexpectedly, we got the hydroxyl amide, which is the product of the ring-
opening of chiral oxazoline involving pyrrolidone (C16H22N2O3). Surprisingly,
copper acetate monohydrate only acted as the Lewis catalyst, so the mechanism can
Fig. 1 The crystal structure of compound I
Fig. 2 The packing diagram of
the unit cell
123

The ring-opening of chiral oxazoline involving pyrrolidone
2737
O
O
O
Cu(OAc)2
H2O
N
O
H+
O
N
O
OH
H2O
N
N
HN
CH2Ph
HN
CH2Ph
CH2Ph
III
O
O
N
N
O
O
-H+
OH2
CH2OH
HN
HN
CH2Ph
CH2Ph
Scheme 2 The proposed mechanism of formation for compound II
be proposed that copper acetate monohydrate activated the C=N bond, then water
?
attacked C2 forming the oxazolinum intermediate III, and finally deprotonation
formed compound II (Scheme 2).
Conclusions
In conclusion, we obtained the crystal structure of the ring-opening of the chiral
oxazoline involving pyrrolidone (compound II), further studies are in progress in
synthesizing our target products of organometallic complexes by changing the
synthetic routes.
Experimental
1H and 13C NMR spectra were obtained using a Bruker AM-300 spectrometer. The
following abbreviations were used to designate chemical shiftmutiplicities:
s = singlet, d = doublet, t = triplet, m = multiplet. Infrared spectra were recorded
on a Mattson Galaxy Series FTIR 3000 spectrometer, and optical rotations were
measured with a WZZ-1 autometer.
Preparation of 1-[2-(benzyl-4,5-dihydro-oxazol-2-yl)-ethyl]-pyrrolidin-2-one
Two grams of dry ZnCl2 (7.8 mmol), 3-(2-oxo-pyrrolidin-1-yl) propionitrile 6.5 g
(47.1 mmol) and L-amino alcohol (60.0 mmol) were added under free-water and
free-oxygen condition to a dry 100-mL Schlenk flask. They were dissolved in
60 mL of dry chlorobenzene, the reaction mixture was refluxed for 72 h. The
solvent was removed under reduced pressure and the residue was dissolved in
15 mL H2O, extracted with 30 9 3 mL of dichloromethane. The solvent was then
123

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L. Mei et al.
removed under vacuum, ggiving a crude red oil. Further purification was performed
by silica gel (petroleum ether/dichlormethane 4/1). Red brown liquid, yield: 72 %;
5
[a] = ?31.58 (c = 0.285, CH2Cl2): 1H NMR (300 MHz, CDCl3, 27 °C), d
D
(ppm) = 7.17 * 7.26 (m, 5H), 4.32 * 4.35 (m, 1H), 4.14 (t, J = 0.3 Hz, 1H),
3.91 * 3.9 5 (m, 1H), 3.50 * 3.57 (m, 2H), 3.36 * 3.40 (m, 3H), 3.06 * 3.08
(m, 1H), 2.51 * 2.63 (m, 3H), 2.31 * 2.33 (m, 2H), 1.97 (t, J = 0.6 Hz, 2H); 13
C
NMR, 22.59, 22.81, 25.34, 45.47, 64.87, 72.89, 114.34, 117.71, 118.12, 128.64,
129.11, 146.38, 163.33 IR (KBr): 3,427, 3,060, 3,027, 2,966, 1,734, 1,682, 1,603,
1,496, 1,454, 1,379, 1,288, 1,226, 1,176, 983, 923, 852, 753, 703, 655, 565, 497.
HRMS (EI): m/z (%): calc. for C16H20N2O2:272.1525; found: 272.1523.
N-[1-Benzyl-2-hydroxy]ethyl-3-[2-oxo-pyrrole]propionamide
1-[2-[(4S)-4,5-Dihydro-4-(phenylmethyl)-2-oxazolyl]ethyl]-2-pyrrolidone
0.50 g
(1.83 mmol) (compound I)reacted withcopperacetate monohydrate 0.3 g (1.50 mmol)
in ethanol under refluxing for 48 h, then after recrystallizing with ethanol and hexane,
brown crystals were obtained, yield: 47 %, [a] 5D = -11.68 (c = 0.086, C2H5OH): 1H
NMR(500 MHz,CDCl3, 27 °C), d(ppm) = 7.17 * 7.27(m, 5H),6.91(s, 1H),4.16(s,
1H), 3.28 * 3.70 (m, 8H), 2.84 * 2.85 (m, 2H), 2.30 * 2.43 (m, 5H), 1.94 * 1.98
(m, 3H). 13C NMR (75 MHz, CDCl3) 73.22, 65.16, 62.98, 57.30, 55.21, 46.04, 43.55,
24.90, 24.12, 22.58, 22.43, 21.74. IR: 3,300, 2,941, 2,849, 1,715, 1,669, 1,556, 1,496,
1,472, 1,453, 1,430, 1,377, 1,292, 1,256, 1,227, 1,208, 1,163, 1,080, 1,057, 1,044, 1,008,
974, 754, 705, 627, 535, 498. elemental analysis: C16H22N2O3, found: C:66.53 %,
N:9.42, H:7.594; calc. C:66.18 %, N:9.65, H:7.64.
Structure determination
The prismatic colorless crystal of the title compound II of approximately
0.315 9 0.308 9 0.213 mm was selected for data collection on a ‘‘graphite’’
´
˚
diffractometer with mirror monochromated MoK/a radiation (k = 0.71073A). A
total of 3,029 reflections were collected in the range of 5.281 \ h \ 45.651° by
using the ‘‘phi and omega scans’’ techniques at 293(2) K, C16H22N2O3,
´
˚
M = 290.36, monoclinic, P 21 21 21, a = 8.2743(9)A, a = 908, b = 8.7148(9)
´
´
´
3
˚
A, b = 908, c = 21.319(2) A, c = 908, V = 1537.3(3) A , Z = 4, Dcalc. = 1.255 g/m3,
the final R factor was R1 = 0.0423, 2752 for reflections with I0 [2r(I0), Rx = 0.0980
for all data, The structure wwas solved by full-matrix least-squares on F2 using the
SHELXTL PROGRAM [8–10].
˚
˚
Supplementary material has been deposited with the Cambridge Crystallographic
Data Centre (no. CCDC 853716); deposit@ccdc.cam.ac.uk or http://www.ccdc.
cam.ac.uk).
References
1. K. Motokura, N. Nakagiri, K. Mori, T. Mizugaki, K. Ebitani, K. Jitsukawa, K. Kaneda, Org. Lett.
8(20), 4617–4620 (2006)
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2. C.B. Wu, J.Y. Hao, X.M. Deng, J. Polym. Res. 17(6), 869–876 (2010)
3. M. Hocquaux, B. Marcot, G. Redeuilh, C. Viel, M. Brunaud, J. Navarro, C. Lacour, C. Cazaubon,
Eur. J. Med. Chem. 18(4), 319–329 (1983)
4. J.E. Dubois, C.C.R. Lion, Hebd. Seances Acad. Sci. 274, 303 (1972)
5. H. Vorbru¨ggen, K. Krolikiewicz, Tetrahedron 49, 9353 (1993)
6. A. Cwik, Z. Hell, A. Hegedu¨s, Z. Finta, Z. Horvath, Tetrahedron Lett. 43, 3985 (2002)
7. M. Luo, Chin. J. Struct. Chem. 28(10), 1286–1289 (2009)
8. G.M. Sheldrick, SHELXS-97, program for X-ray crystal structure solution (University of Gottingen,
Germany, 1997)
9. G.M. Sheldrick, SHELXL-97, program for X-ray crystal structure (University of Gottingen,
Germany, 1997)
10. G.H. Stout, L.H. Jensen, X-ray structure determination: a practical guide (MacMillan, New York,
1968)
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