Synthesis of novel 4-functionalised oxazolidin-2-ones

Article abstract of DOI:10.1055/s-2005-865292

The synthesis of O-substituted and O-unsubstituted 3-hydroxy-4-thioxo- oxazolidin-2-ones, functionalised 4-imino-oxazolidine-2-ones and 4-phenoxy-imino-oxazolidin-2-one starting from O-substituted and O-unsubstituted 3-hydroxy-4-imino-oxazolidin-2-ones is described. A one-pot protocol for the preparation of 4-methoxyimino-, 4-aralkoxyimino- and 4-phenoxyimino-oxazolidin- 2-ones has been developed. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-865292

1340
PAPER
Synthesis of Novel 4-Functionalised Oxazolidin-2-ones
Synthesis of
N
ove
h
l
4-Functiona
a
lised Oxaz
l
olidin-2
i
-one
s
d Widyan, Thomas Kurz*
Institute of Pharmacy, University of Hamburg, Bundesstrasse 45, 20146 Hamburg, Germany
Fax +49(40)428386573; E-mail: kurz@chemie.uni-hamburg.de
Received 19 November 2004; revised 3 January 2005
This paper is dedicated to Prof. Dr. D. Geffken.
O
Abstract: The synthesis of O-substituted and O-unsubstituted 3-
hydroxy-4-thioxo-oxazolidin-2-ones, functionalised 4-imino-ox-
O
O
N
N
H
azolidine-2-ones and 4-phenoxy-imino-oxazolidin-2-one starting
from O-substituted and O-unsubstituted 3-hydroxy-4-imino-oxazo-
lidin-2-ones is described. A one-pot protocol for the preparation of
4-methoxyimino-, 4-aralkoxyimino- and 4-phenoxyimino-oxazoli-
din-2-ones has been developed.
O
N
CH3
O
O
O
Famoxadone
Trimethadione
Key words: heterocycles, oxazolidin-2-ones, Dimroth rearrange-
ment, thionation, ring closure
O
O
Oxazolidin-2,4-diones and their 4-imino(thioxo) ana-
logues have attracted much attention in medicinal and ag-
ricultural chemistry. Famoxadone (Figure 1), a 3-
phenylamino-oxazolidin-2,4-dione, is a broad spectrum
fungicide, which is particularly active against grape
downy mildew and potato and tomato late and early
blights.1 Vinclozolin represents a well known dicarbox-
imide fungicide used for the control of Botrytis and Slero-
tina spp.2 Trimethadione, is an anticonvulsant for the
treatment of epilepsy.3 Geffken reported the synthesis and
fungicidal activity of 4-hydroxyimino-oxazolidin-2-ones,
which have been obtained by treatment of 4-alkoxy-3-ox-
azolin-2-ones with hydroxylamine.4 Furthermore, in 1992
DuPont described 3-phenylamino-4-imino(thioxo)-ox-
azolidin-2-ones as novel classes of fungicides.5 Surpris-
ingly, the corresponding O-substituted and O-
unsubstituted 3-hydroxy-4-imino(thioxo)-oxazolidin-2-
ones have not been reported so far.
O
NH
O
N
N
H
NOH
X
X: NH, S
Figure 1 Selected biologically active oxazolidin-2,4-diones and
analogues.
Recently, we reported the first synthesis of O-substituted
and O-unsubstituted 3-hydroxy-4-imino-oxazolidin-2-
ones 1 and their sodium methoxide-mediated conversion
into the corresponding a-hydroxyamidoximes.6 We now
describe the synthetic potential of 1 as precursors in the
preparation of novel 4-functionalised oxazolidin-2-one
derivatives (Scheme 1).
Thionation of substrates 1a–l by hydrogen sulfide in an-
hydrous CH2Cl2 in the presence of pyridine afforded pre-
viously unreported O-substituted and O-unsubstituted 3-
hydroxy-4-thioxo-oxazolidin-2-ones (2a–l) in good
yields of 75–85% (Scheme 1, Table 1).5
Scheme 1 Synthesis of 4-functionalised oxazolidin-2-ones.
Reactions of 1b with phenyl isocyanate, 4-fluorophenyl
isothiocyanate, p-toluenesulfonyl chloride and 4-fluo-
robenzoyl chloride furnished the derivatised 4-imino-ox-
azolidin-2-ones 3a–d in 68–80% yield (Scheme 1).
Treatment of 1c with Et3N in CH2Cl2 provided, in accor-
dance with previous studies, the Dimroth rearrangement
product 4c in 93% yield (Scheme 1).7,8
SYNTHESIS 2005, No. 8, pp 1340–1344
Advanced online publication: 07.04.2005
x
x
.
x
x
.2
0
0
5
DOI: 10.1055/s-2005-865292; Art ID: T13804SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Novel 4-Functionalised Oxazolidin-2-ones
1341
Table 1 3-Alkoxy-, 3-Aralkoxy-, 3-Phenoxy- and 3-Hydroxy-4-
thioxo-oxazolidin-2-ones 2a–l
Table 2 4-Methoxyimino-, 4-Aralkoxyimino- and 4-Phenoxyimi-
no-oxazolidin-2-ones (4a–e)
2
a
b
c
d
e
f
R1
R2
Yield (%)
4
a
b
c
R2
Yield (%)
Ph2CH
Ph2CH
Ph2CH
Ph2CH
Ph2CH
Ph2CH
t-Bu
Me
78
85
80
75
83
80
75
84
75
80
81
75
Me
70
75
73
80
72
Bn
Bn
Ph
Ph
t-Bu
Ph(CH2)2
H
d
e
Ph(CH2)2
Ph(CH2)3
more, we have developed a new and operationally simple
one-pot protocol for the synthesis of 4-alkoxyimino-, 4-
aralkoxyimino-, and 4-phenoxyimino-oxazolidin-2-ones.
This method complements Geffken’s multi-step synthesis
of 4-hydroxyimino-oxazolidin-2-ones and offers advan-
tages in convenience and yields.
g
h
i
Me
t-Bu
Bn
t-Bu
Ph
j
t-Bu
t-Bu
Ph(CH2)2
H
k
l
t-Bu
Melting points (uncorrected) were determined on a Mettler FP 62
apparatus. Elemental analyses were carried out with a Heraeus
CHN-O-Rapid instrument. IR spectra were recorded on a Shimadzu
FT-IR 8300 spectrometer. 1H NMR (400 MHz) and 13C NMR (100
MHz) spectra were recorded on a Bruker AMX 400 spectrometer
using TMS as an internal standard and DMSO-d6 as solvent.
t-Bu
The smooth conversion of 1c into 4c prompted us to de-
velop the first one-pot protocol for the synthesis of 4-
methoxyimino-, 4-aralkoxyimino- and 4-phenoxyimino-
oxazolidin-2-ones (4a–e) (Scheme 2). Successive treat-
ment of cyanohydrins with 1,1¢-carbonyldiimidazole
(CDI) and O-substituted hydroxylamines furnished inter-
mediates 1, which upon treatment with Et3N underwent
Dimroth rearrangement to give 4a–e in good yields of 70–
80% (Table 2).9 Discrimination between the structures of
Preparation of 2a–l; General Procedure
H2S gas was introduced for 30 min to a solution of 1a–l (3 mmol)
in anhyd CH2Cl2 (20 mL) and anhyd pyridine (12 mL). After stir-
ring at r.t. for 3 h the reaction mixture was diluted with Et2O (50
mL) and washed thrice with 20% HCl (15 mL). The organic layer
was dried over MgSO4 and the solvent was evaporated to afford 2a–
l as yellow solids, which were recrystallised from Et2O–hexane.
compounds 1 and 4 was accomplished by IR, 1H and 13
NMR spectroscopy.
C
5-Benzhydryl-3-methoxy-4-thioxo-oxazolidin-2-one (2a)
Yield: 0.73 g (78%); yellow solid; mp 75 °C.
IR (KBr): 1280, 1809 cm–1.
1H NMR (DMSO-d6): d = 3.45 (s, 3 H), 4.76 (d, J = 2.80 Hz, 1 H),
5.84 (d, J = 2.54 Hz, 1 H), 7.21–7.43 (m, 10 H).
13C NMR (DMSO-d6): d = 54.3, 64.2, 88.1, 127.2, 127.7, 128.4,
128.8, 129.0, 130.1, 137.8, 140.8, 151.2, 192.5.
Anal. Calcd for C17H15NO3S: C, 65.16; H, 4.82; N, 4.47. Found: C,
65.01; H, 5.01; N, 4.35.
5-Benzhydryl-3-benzyloxy-4-thioxo-oxazolidin-2-one (2b)
Yield: 0.99 g (85%); yellow solid; mp 112 °C.
IR (KBr): 1275, 1810 cm–1.
1H NMR (DMSO-d6): d = 4.66 (q, J = 9.76 Hz, 2 H), 4.95 (d, J =
2.80 Hz, 1 H), 6.15 (d, J = 2.54 Hz, 1 H), 7.21–7.44 (m, 15 H).
13C NMR (DMSO-d6): d = 53.6, 78.3, 88.2, 126.8, 127.5, 128.2,
128.6, 128.95, 129.02, 129.9, 130.09, 130.11, 132.9, 136.6, 140.0,
151.4, 194.4.
Scheme 2 One-pot synthesis of 4-methoxy-, 4-aralkoxy-, and 4-
phenoxyimino-oxazolidin-2-ones (4a–e).
Anal. Calcd for C23H19NO3S: C, 70.93; H, 4.92; N, 3.60. Found: C,
70.80; H, 5.03; N, 3.49.
The structures of all compounds (2–4) were elucidated by
5-Benzhydryl-3-phenoxy-4-thioxo-oxazolidin-2-one (2c)
Yield: 0.90 g (80%); yellow solid; mp 120 °C.
IR, 1H, 13C NMR spectroscopy and elemental analysis.
In conclusion, we have synthesised a variety of novel 4-
functionalised oxazolidin-2-one derivatives as analogues
of existing biologically active oxazolidin-2-ones. Further-
IR (KBr): 1276, 1815 cm–1.
1H NMR (DMSO-d6): d = 4.82 (d, J = 2.81 Hz, 1 H), 6.10 (d, J =
2.54 Hz, 1 H), 7.11–7.45 (m, 15 H).
Synthesis 2005, No. 8, 1340–1344 © Thieme Stuttgart · New York

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K. Widyan, T. Kurz
PAPER
13C NMR (DMSO-d6): d = 53.0, 87.9, 126.8, 127.5, 128.2, 128.6,
128.95, 129.02, 129.9, 130.1, 132.9, 136.6, 140.0, 153.6, 194.4.
1H NMR (DMSO-d6): d = 0.92 (s, 9 H), 4.71 (s, 1 H), 7.22–7.50 (m,
5 H).
Anal. Calcd for C22H17NO3S: C, 70.38; H, 4.56; N, 3.73. Found: C,
70.24; H, 4.68; N, 3.55.
13C NMR (DMSO-d6): d = 27.6, 36.1, 86.6, 126.9, 129.7, 130.5,
134.1, 151.9, 194.0.
Anal. Calcd for C13H15NO3S: C, 58.85; H, 5.70; N, 5.28. Found: C,
58.70; H, 5.93; N, 5.09.
5-Benzhydryl-3-tert-butoxy-4-thioxo-oxazolidin-2-one (2d)
Yield: 0.80 g (75%); yellow solid; mp 73 °C.
IR (KBr): 1275, 1810 cm–1.
3-tert-Butoxy-5-tert-butyl-4-thioxo-oxazolidin-2-one (2j)
Yield: 0.60 g (80%); yellow solid; mp 65 °C.
IR (KBr): 1270, 1807 cm–1.
1H NMR (DMSO-d6): d = 0.94 (s, 9 H), 4.66 (d, J = 2.81 Hz, 1 H),
5.84 (d, J = 2.58 Hz, 1 H), 7.21–7.43 (m, 10 H).
13C NMR (DMSO-d6): d = 26.5, 52.6, 79.2, 88.1, 127.2, 127.7,
1H NMR (DMSO-d6): d = 0.91 (s, 9 H), 1.10 (s, 9 H), 4.71 (s, 1 H).
13C NMR (DMSO-d6): d = 27.6, 28.0, 36.1, 75.7, 86.6, 153.5, 194.4.
128.4, 128.8, 129.0, 130.1, 137.8, 140.8, 152.2, 193.9.
Anal. Calcd for C20H21NO3S: C, 67.58; H, 5.95; N, 3.94. Found: C,
67.65; H, 6.00; N, 3.85.
Anal. Calcd for C11H19NO3S: C, 53.85; H, 7.81; N, 5.71. Found: C,
53.90; H, 7.80; N, 5.75.
5-Benzhydryl-3-phenylethoxy-4-thioxo-oxazolidin-2-one (2e)
Yield: 1.00 g (83%); yellow solid; mp 101 °C.
IR (KBr): 1270, 1815 cm–1.
1H NMR (DMSO-d6): d = 2.95 (t, J = 6.87 Hz, 2 H), 4.19 (t, J = 7.12
Hz, 2 H), 4.95 (d, J = 2.80 Hz, 1 H), 6.15 (d, J = 2.54 Hz, 1 H), 7.21–
7.44 (m, 15 H).
13C NMR (DMSO-d6): d = 35.5, 53.6, 77.4, 88.2, 126.8, 127.5,
128.2, 128.6, 128.95, 129.02, 129.8, 130.09, 130.11, 132.9, 136.6,
140.0, 151.4, 192.8.
5-tert-Butyl-3-phenylethoxy-4-thioxo-oxazolidin-2-one (2k)
Yield: 0.71 g (81%); yellow solid; mp 93 °C.
IR (KBr): 1275, 1810 cm–1.
1H NMR (DMSO-d6): d = 0.90 (s, 9 H), 2.95 (t, J = 6.87 Hz, 2 H),
4.19 (t, J = 7.12 Hz, 2 H), 4.73 (s, 1 H), 7.20–7.45 (m, 5 H).
13C NMR (DMSO-d6): d = 27.6, 34.4, 36.1, 76.6, 88.3, 126.9, 129.7,
130.5, 134.1, 153.9, 194.0.
Anal. Calcd for C15H19NO3S: C, 61.41; H, 6.53; N, 4.77. Found: C,
61.35; H, 6.60; N, 4.70.
Anal. Calcd for C24H21NO3S: C, 71.44; H, 5.25; N, 3.47. Found: C,
71.30; H, 5.45; N, 3.29.
5-tert-Butyl-3-hydroxy-4-thioxo-oxazolidin-2-one (2l)
Yield: 0.43 g (75%); yellow solid; mp 175 °C.
IR (KBr): 1270, 1810 cm–1.
5-Benzhydryl-3-hydroxy-4-thioxo-oxazolidin-2-one (2f)
Yield: 0.72 g (80%); yellow solid; mp 190 °C.
1H NMR (DMSO-d6): d = 0.98 (s, 9 H), 4.78 (s, 1 H).
13C NMR (DMSO-d6): d = 24.6, 34.1, 88.5, 152.9, 193.9.
IR (KBr): 1270, 1805 cm–1.
1H NMR (DMSO-d6): d = 4.65 (d, J = 2.81 Hz, 1 H), 5.90 (d, J =
2.54 Hz, 1 H), 7.00–7.45 (m, 10 H).
13C NMR (DMSO-d6): d = 51.2, 88.2, 127.0, 127.5, 128.5, 128.7,
129.8, 137.7, 138.0, 140.8, 151.1, 194.1.
Anal. Calcd for C7H11NO3S: C, 44.43; H, 5.86; N, 7.40. Found: C,
44.20; H, 6.00; N, 7.18.
Preparation of 3a,b; General Procedure
Anal. Calcd for C16H13NO3S: C, 64.20; H, 4.38; N, 4.68. Found: C,
63.95; H, 4.52; N, 4.50.
Phenyl isocanate or 4-fluorophenyl isothiocyanate (3 mmol) was
added to a solution of 1b (1.11 g, 3 mmol) in anhy THF (5 mL) un-
der ice cooling and the reaction mixture was stirred at r.t. for 3 h.
The solvent was evaporated under reduced pressure and the remain-
ing oil was crystallised from EtOAc–hexane to afford 3a,b as co-
lourless solids.
5-tert-Butyl-3-methoxy-4-thioxo-oxazolidin-2-one (2g)
Yield: 0.46 g (75%); yellow solid; mp 67 °C.
IR (KBr): 1280, 1809 cm–1.
1H NMR (DMSO-d6): d = 0.90 (s, 9 H), 3.45 (s, 3 H), 4.66 (s, 1 H).
13C NMR (DMSO-d6): d = 24.6, 34.2, 64.4, 88.6, 152.9, 194.0.
N-(5-Benzhydryl-3-benzyloxy-4-oxazolidinylidene)-N′-phenyl-
urea (3a)
Yield: 1.18 g (80%); colourless solid; mp 120 °C.
IR (KBr): 1695, 1720, 1810 cm–1.
Anal. Calcd for C8H13NO3S: C, 47.27; H, 6.45; N, 6.89. Found: C,
47.20; H, 6.68; N, 6.63.
1H NMR (DMSO-d6): d = 4.67 (q, J = 10.18 Hz, 2 H), 4.75 (d, J =
2.90 Hz, 1 H), 5.97 (d, J = 2.60 Hz, 1 H), 7.20–7.55 (m, 20 H), 7.66
(s, 1 H).
13C NMR (DMSO-d6): d = 53.6, 78.4, 88.2, 126.8, 127.5, 128.5,
128.6, 128.8, 128.95, 129.01, 129.9, 130.0, 130.2, 132.9, 136.6,
140.0, 151.4, 154.0, 167.0.
3-Benzyloxy-5-tert-butyl-4-thioxo-oxazolidin-2-one (2h)
Yield: 0.70 g (84%); yellow solid; mp 60 °C.
IR (KBr): 1273, 1815 cm–1.
1H NMR (DMSO-d6): d = 0.91 (s, 9 H), 4.70 (s, 1 H), 5.07 (q, J =
10.68 Hz, 2 H), 7.88–7.55 (m, 5 H).
13C NMR (DMSO-d6): d = 24.5, 34.8, 78.5, 84.0, 126.9, 129.7,
120.5, 134.1, 151.8, 194.3.
Anal. Calcd for C30H25N3O4: C, 73.31; H, 5.13; N, 8.55. Found: C,
73.20; H, 5.00; N, 8.41.
Anal. Calcd for C14H17NO3S: C, 60.19; H, 6.13; N, 5.01. Found: C,
59.90; H, 6.39; N, 4.85.
N-(5-Benzhydryl-3-benzyloxy-2-oxo-oxazolidin-4-ylidene)-3-
(fluorophenyl)thiourea (3b)
Yield: 1.07 g (68%); colourless solid; mp 102 °C.
IR (KBr): 1690, 1810 cm–1.
5-tert-Butyl-3-phenoxy-4-thioxo-oxazolidin-2-one (2i)
Yield: 0.60 g (75%); yellow solid; mp 87 °C.
IR (KBr): 1277, 1816 cm–1.
Synthesis 2005, No. 8, 1340–1344 © Thieme Stuttgart · New York

PAPER
Synthesis of Novel 4-Functionalised Oxazolidin-2-ones
1343
1H NMR (DMSO-d6): d = 4.60 (q, J = 10.18 Hz, 2 H), 4.77 (d, J =
2.90 Hz, 1 H), 5.90 (d, J = 2.61 Hz, 1 H), 7.21–7.50 (m, 19 H), 7.70
(s, 1 H).
13C NMR (DMSO-d6): d = 53.6, 78.3, 87.9, 126.7, 127.0, 128.2,
128.6, 128.8, 129.0, 129.1, 130.0, 130.1, 130.2, 133.0, 136.6, 141.0,
151.5, 154.1, 191.5.
1H NMR (DMSO-d6): d = 3.80 (s, 3 H), 4.82 (d, J = 4.71 Hz, 1 H),
6.10 (d, J = 4.59 Hz, 1 H), 7.15–7.49 (m, 10 H), 11.52 (s, 1 H).
13C NMR (DMSO-d6): d = 35.3, 52.7, 66.0, 78.9, 112.6, 120.9,
122.6, 127.3, 129.0, 129.8, 130.1, 140.7, 151.7, 154.0.
Anal. Calcd for C17H16N2O3: C, 68.91; H, 5.44; N, 9.45. Found: C,
68.95; H, 5.43; N, 9.53.
Anal. Calcd for C30H24FN3O3S: C, 68.56; H, 4.60; N, 7.99. Found:
C, 68.42; H, 4.71; N, 7.89.
5-Benzhydryl-4-benzyloxyimino-oxazolidin-2-one (4b)
Yield: 1.40 g (75%); colourless solid; mp 130 °C.
Preparation of 3c,d; General Procedure
IR (KBr): 1760, 1665 cm–1.
p-Toluenesulfonyl chloride or 4-fluorobenzoyl chloride (3 mmol)
was added to a solution of 1b (1.11 g, 3 mmol) and Et3N (3 mmol)
in anhyd THF (5 mL) under ice cooling. The reaction mixture was
stirred at r.t. for 3 h and the solvent was evaporated under reduced
pressure. The remaining oil was dissolved in EtOAc (20 mL) and
the solution was washed with water. (5 mL). The organic layer was
dried over MgSO4, the solvent evaporated and the resulting oil was
crystallised from EtOAc–hexane.
1H NMR (DMSO-d6): d = 4.62 (s, 2 H), 4.91 (d, J = 4.70 Hz, 1 H),
5.90 (d, J = 4.60 Hz, 1 H), 7.15–7.40 (m, 15 H), 11.50 (s, 1 H).
13C NMR (DMSO-d6): d = 53.0, 75.9, 79.0, 112.7, 113.5, 121.0,
122.8, 127.3, 127.8, 128.8, 129.5, 129.8, 130.1, 130.3, 140.5, 151.7,
154.0.
Anal. Calcd for C23H20N2O3: C, 74.18; H, 5.41; N, 7.52. Found: C,
74.35; H, 5.29; N, 7.33.
N-(5-Benzhydryl-3-benzyloxy-2-oxo-oxazolidin-4-ylidene)-4-
methylbenzenesulfonamide (3c)
Yield: 1.11 g (70%); colourless solid; mp 160 °C.
IR (KBr): 1695, 1795 cm–1.
1H NMR (DMSO-d6): d = 3.32 (s, 3 H), 4.62 (q, J = 10.18 Hz, 2 H),
4.70 (d, J = 2.90 Hz, 1 H), 5.97 (d, J = 2.60 Hz, 1 H), 7.18–7.45 (m,
19 H).
13C NMR (DMSO-d6): d = 53.7, 78.4, 87.8, 112.1, 126.7, 127.4,
128.5, 128.7, 128.9, 129.0, 129.1, 129.8, 130.1, 130.2, 132.9, 136.7,
140.0, 151.3, 156.0.
5-Benzhydryl-4-phenoxyimino-oxazolidin-2-one (4c)
Yield: 1.31 g (73%); colourless solid; mp 189 °C.
IR (KBr): 1760, 1670 cm–1.
1H NMR (DMSO-d6): d = 4.79 (q, J = 4.70 Hz, 1 H), 6.14 (d, J =
4.60 Hz, 1 H), 7.10–7.50 (m, 15 H), 11.00 (s, 1 H).
13C NMR (DMSO-d6): d = 52.5, 78.4, 112.6, 113.1, 120.9, 122.7,
127.0, 127.6, 128.8, 129.4, 129.7, 130.0, 130.3, 140.8, 151.6, 154.0.
Anal. Calcd for C22H18N2O3: C, 73.73; H, 5.06; N, 7.82. Found: C,
73.82; H, 4.91; N, 7.64.
Anal. Calcd for C30H26N2O5S: C, 68.42; H, 4.98; N, 5.32. Found: C,
68.20; H, 5.09; N, 5.23.
5-Benzhydryl-4-phenylethyloxyimino-oxazolidin-2-one (4d)
Yield: 1.55 g (80%); colourless solid; mp 110 °C.
IR (KBr): 1758, 1667 cm–1.
N-(5-Benzhydryl-3-benzyloxy-2-oxo-oxazolidin-4-ylidene)-4-
fluorobenzamide (3d)
Yield: 1.16 g (78%); colourless solid; mp 173 °C.
IR (KBr): 1670, 1690, 1790 cm–1.
1H NMR (DMSO-d6): d = 2.90 (t, J = 6.80 Hz, 2 H), 4.20 (t, J = 6.80
Hz, 2 H), 4.92 (d, J = 4.70 Hz, 1 H), 5.93 (d, J = 4.60 Hz, 1 H), 7.10–
7.40 (m, 15 H), 11.23 (s, 1 H).
13C NMR (DMSO-d6): d = 35.5, 51.5, 74.6, 78.8, 112.6, 120.7,
122.6, 127.8, 128.5, 128.8, 129.4, 129.8, 130.2, 137.5, 140.5, 151.6,
154.0.
1H NMR (DMSO-d6): d = 4.60 (q, J = 10.17 Hz, 2 H), 4.75 (d, J =
2.90 Hz, 1 H), 5.95 (d, J = 2.60 Hz, 1 H), 7.21–7.50 (m, 19 H).
13C NMR (DMSO-d6): d = 53.5, 78.4, 87.9, 111.9, 126.8, 127.4,
128.4, 128.6, 128.8, 128.9, 129.3, 129.9, 130.0, 130.3, 132.9, 136.7,
140.1, 151.4, 154.1, 168.1.
Anal. Calcd for C24H22N2O3: C, 74.59; H, 5.74; N, 7.25. Found: C,
74.45; H, 5.83; N, 7.03.
Anal. Calcd for C30H23FN2O4: C, 70.86; H, 4.69; N, 5.66. Found: C,
72.95; H, 4.80; N, 5.50.
5-Benzhydryl-4-phenylpropyloxyimino-oxazolidin-2-one (4e)
Yield: 1.44 g (72%); colourless solid; mp 107 °C.
IR (KBr): 1760, 1672 cm–1.
Preparation of 4a–e; General Procedure
A solution of cyanohydrine (5 mmol) in anhyd CH2Cl2 (5 mL) was
added dropwise over a period of 10 min to a suspension of 1,1¢-car-
bonyldiimidazole (0.89 g, 5.5 mmol) in CH2Cl2 (5 mL) under ice
cooling. After stirring at r.t. for 10 min a solution of the appropriate
O-substituted hydroxylamine (5 mmol) in anhyd CH2Cl2 (5 mL)
was added and the reaction mixture was stirred at r.t. for 1 h. The
reaction mixture was concentrated under reduced pressure, Et3N (3
mL) was added and the mixture was heated to 60–70 °C until two
sharp bands in the IR spectrum appeared at 1745–1760 and 1650–
1680 cm–1. After cooling to r.t., the reaction mixture was diluted
with Et2O, washed with brine and water. The organic layer was
dried over MgSO4, filtered, concentrated and the remaining oil was
crystallised from Et2O–hexane.
1H NMR (DMSO-d6): d = 1.90–2.00 (m, 2 H), 2.70 (t, J = 7.56 Hz,
2 H), 4.08 (t, J = 6.5 Hz, 2 H), 4.90 (d, J = 4.70 Hz, 1 H), 6.03 (d,
J = 4.60 Hz, 1 H), 7.00–7.39 (m, 15 H), 11.34 (s, 1 H).
13C NMR (DMSO-d6): d = 30.6, 31.7, 52.7, 73.7, 79.0, 112.6, 120.7,
122.7, 127.8, 128.5, 128.9, 129.5, 129.8, 130.2, 137.6, 140.3, 151.7,
153.8.
Anal. Calcd for C25H24N2O3: C, 74.98; H, 6.04; N, 6.99. Found: C,
75.09; H, 5.92; N, 7.20.
References
(1) (a) Tomlin, C. D. S. The Pesticide Manual, 12th ed.; BCPC
Publications: Alton UK, 2000, 375. (b) Sternberg, J. A.;
Geffken, D.; Adams, J. B.; Jordan, D. B.; Sternberg, C. G.;
Campbell, C. L.; Moberg, W. K.; Livingston, R. S. Synthesis
and Chemistry of Agrochemicals, ACS Symposium Series
5-Benzhydryl-4-methoxyimino-oxazolidin-2-one (4a)
Yield: 1.04 g (70%); colourless solid; mp 101 °C.
IR (KBr): 1755, 1660 cm–1.
Synthesis 2005, No. 8, 1340–1344 © Thieme Stuttgart · New York

1344
K. Widyan, T. Kurz
PAPER
Hydroxyimino-oxazolidin-2-onen; Universität Hamburg:
686; American Chemical Society: Washington DC, 1998,
216.
Germany, 1999.
(2) Tomlin, C. D. S. The Pesticide Manual, 12th ed.; BCPC
Publications: Alton UK, 2000, 956.
(3) Thueson, D. O.; Withrow, C. D.; Giam, C. S.; Woodbury, D.
M. Epilepsia 1974, 15, 563.
(4) (a) Geffken, D.; Riederer, C. Sci. Pharm. 2001, 69, 265.
(b) Riederer, C. PhD Dissertation: Zur Synthese von
Tetrahydro-oxazolo-[4,3-c]-1,2,4-oxadiazol-5-onen und
Tetrahydro-oxazolo-[4,3-c]-1,2,4-oxadiazin-6-onen aus 4-
(5) Sternberg, J. A.; Adams, J. B. DuPont de Nemours, EP
503798, 1992; Chem. Abstr. 1993, 118, 80921u.
(6) Kurz, T.; Widyan, K. Org. Lett. 2004, 6, 4403.
(7) Kurz, T.; Geffken, D.; Widyan, K. Tetrahedron 2004, 60,
2409.
(8) Kurz, T.; Widyan, K.; Wackendorff, C.; Schlüter, K.
Synthesis 2004, 1987.
(9) Kurz, T.; Widyan, K. Org. Biomol. Chem. 2004, 2, 2023.
Synthesis 2005, No. 8, 1340–1344 © Thieme Stuttgart · New York