SHORT PAPER
3111
An Excellent Procedure for the Synthesis of Oxazolidin-2-ones
Synthesis of
O
xazo
e
lidin-2-one
o
s
rge Bratulescu*
Faculty of Chemistry, University of Craiova, 13 A.I. Cuza, 200396 Craiova, Romania
E-mail: georgebratulescu@yahoo.com
Received 29 June 2007; revised 24 July 2007
Table 1 Oxazolidin-2-one Derivatives 3a
Abstract: Synthesis of oxazolidin-2-ones derivatives was carried
out starting from urea and ethanolamine reagents using microwave
irradiation in a chemical paste medium.
Product R1
R2
Time
(min)
Yield
(%)
Mp
(°C)
Key words: ethanolamines, urea, microwave, condensation, ox-
azolidin-2-one
3a
H
H
4
97
90 (Lit.9
86.5–88.5)
3b
3c
3d
3e
H
t-Bu
5
91
95
87
81
82
86
93
118
39–40
112
146
128
136
135
The synthesis of oxazolidin-2-ones has been performed
by procedures that involve organic solvents1–4 and expen-
sive metallic catalysts.5–8 These experimental conditions
require long reaction times,9–13 but the yields are less than
satisfactory and many waste products are produced.1–5
Et
H
H
4,5
5
1-naphthyl
H
2-naphthyl
5
Despite these synthetic disadvantages, oxazolidinone de- 3f
H
Cy
H
4
rivatives are important heterocyclic compounds that are
3g
Cy
H
4
useful as inhibitors of animal cell motility and growth,14
possible sphingomyelinase inhibitors,15 inhibitors of the
3h
Ph
5
cytochrome P-450 enzyme aromatase,2,16 drugs with anti-
a Satisfactory microanalysis obtained: C 0.03%; H 0.06%;
0.02%.
bacterial activity against methicillin-resistant Staphylo-
N
coccus aureus and Bacillus anthracis,17,18 and fungicidal
pest control agents.19
We have previously utilized microwave-chemical activa-
tion for the synthesis of new organic compounds.20–23
Therefore, we realized a procedure for the synthesis of ox-
azolidin-2-ones 3 from the condensation of ethanolamine
derivatives 1 and urea (2) (Scheme 1).
Ethanolamines and urea are commercially available substances.
The synthesized products were identified by TLC (silica gel,
EtOH), elemental analysis, and their IR spectra. Melting points
were measured on a Böetius melting point apparatus. The IR spectra
were recorded as KBr pellets with using a Perkin-Elmer 1600 spec-
trophotometer. Elemental analyses were carried out with a Carlo
Erba model 1106 apparatus. An Optiquick Y71 microwave oven
operating at 650 W was employed.
R2
R2
R1
H
N
NH2
OH
+
NH2
NH2
– 2 NH3
R1
O
Oxazolidin-2-ones 3; General Procedure
O
O
The ethanolamine derivative 1 (2 mmol) and urea (2, 2 mmol) were
mixed in a 25 mL Pyrex beaker. A few drops of MeNO2 were added
and the resulting paste was irradiated in a microwave oven (l = 12.2
cm) for the required time. The resulting residue was purified by re-
crystallization (CHCl3–EtOH) to give the oxazolidin-2-ones 3 as
colorless crystals (Tables 1 and 2).
1
2
3
Scheme 1
The synthesis takes place in a paste-like chemical medi-
um. This medium resulted from the addition of a small
amount of polar solvent, nitromethane, which does not re-
act with the reagents.22,23 Nitromethane molecules absorb
the microwaves and generate hot spots in the reaction me-
dium, the hot spots then act like catalytic centers.20,21 As a
result the oxazolidin-2-ones 3 were easily obtained with
short reaction times and high yields. Moreover, simple ex-
perimental apparatus, easy product separation, and high
purity of the compounds are important advantages of this
method.
References
(1) Madesclaire, M.; Coudert, P.; Zaitsev, V. P.; Zaitseva, J. V.
Chem. Heterocycl. Compd. (Engl. Transl.) 2006, 42, 506.
(2) Ahmed, S.; Adat, S.; Murrells, A.; Owen, C. P.; Amanuel, Y.
Bioorg. Chem. 2002, 30, 315.
(3) Sudo, A.; Morioka, Y.; Koizumi, E.; Sanda, F.; Endo, T.
Tetrahedron Lett. 2003, 44, 7889.
(4) Peng, X.; Li, F.; Xia, C. Synlett 2006, 1161.
(5) Robles-Machin, R.; Adrio, J.; Carretero, J. C. J. Org. Chem.
2006, 71, 5023.
(6) Li, F.; Xia, C. J. Catal. 2004, 227, 542.
(7) Suga, H.; Suzuki, T.; Inoue, K.; Kakehi, A. Tetrahedron
2006, 62, 9218.
SYNTHESIS 2007, No. 20, pp 3111–3112
Advanced online publication: 21.09.2007
DOI: 10.1055/s-2007-990789; Art ID: Z16107SS
x
x.
x
x
.
2
0
0
7
(8) Tominaga, K.-I.; Sasaki, Y. Synlett 2002, 307.
© Georg Thieme Verlag Stuttgart · New York
Bratulescu, George
