A facile one-pot solid-phase synthesis of oxazolidin-2-ones using polymer-supported 2-hydroxyalkyl selenide reagent

Article abstract of DOI:10.3184/030823407X198267

A simple, efficient and environmentally friendly procedure for one-pot solid-phase synthesis of 2-oxazolidinones in moderate to good yields by reaction of polystyrene-supported 2-hydroxyalkyl selenide with benzoyl isocyanate and subsequent oxidation/cycli

Full text of DOI:10.3184/030823407X198267

74 RESEARCH PAPER
FEBRuARy, 74–75
JOURNAL OF CHEMICAL RESEARCH 2007
A facile one-pot solid-phase synthesis of oxazolidin-2-ones using
polymer-supported 2-hydroxyalkyl selenide reagent
Qiao-Sheng Hua,b, Shou-Ri Shenga,b*, Shu-Ying Lina, Mei-Hong Weia, Qin Xina and
Xiao-Ling Liua
aCollege of Chemistry and Life Science, Gannan Normal University, Ganzhou, 341000, P. R. China
bCollege of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330027, P. R. China
A simple, efficient and environmentally friendly procedure for one-pot solid-phase synthesis of 2-oxazolidinones in
moderate to good yields by reaction of polystyrene-supported 2-hydroxyalkyl selenide with benzoyl isocyanate and
subsequent oxidation/cyclisation-hydrolysis using a selenium traceless linker strategy is described.
Keywords: solid-phase organic synthesis, polymer-supported 2-hydroxyalkyl selenide, 2-oxazolidinones
Polymer-supported organic reagents and catalysts have been
applied to the preparation of organic molecules. The use of
polymer-supported reagents allows the selective removal
of excess reagents and by-products by simple filtration
rather than liquid–liquid extraction and chromatographic
purification. In addition, polymer-supported reagents offer
further advantages that include reaction of active intermediates
by ‘catch-and-release’ selectivity and immobilisation of toxic
intermediates.1 Oxazolidin-2-ones are an interesting class of
compounds because of their various pharmacological effects,2
including antibacterial activity.3 Recently they have also
found application as synthetic intermediates, and as chiral
auxiliaries.4 A survey of the literature reveals a variety of
starting points for the preparation of oxazolidinones including
the reaction of diols with isocyanates, epoxide opening,
amino acids, aziridines, oxetanes, 2-oxazolones, hydroxy
acids or esters, and perhaps the most common, amino
alcohols.5 Although the synthetic routes to oxazolidinones are
well documented, efforts are continuing for the development
of more efficient methods with experimental simplicity.
Organoselenium reagents are now commonly used as a
powerful tool for introducing new functional groups into
organic substrates under extremely mild conditions.6 Recently,
the use of the selenium reagents immobilised on a polymer-
resin has provided significant advantages, including decreased
volatility and simplification of the product work-up.7 In
connection with our interest in solid-phase organoselenium
chemistry.8 We now report a convenient and efficient solid-
phase synthetic approach to oxazolidin-2-ones based on the
polymer-supported 2-hydroxyalkyl selenide 3 (Scheme 1).
The resins 3 were easily prepared in a few steps from cross-
linked (1%) polystyrene by reaction of polystyrene-supported
lithium selenide 2 with different epoxides.8d The IR Spectra of
resins 3 showed large hydroxyl absorptions near at 3600 cm-1
and 3380 cm-1, and bands (C–O) at 1065–1080 cm-1. Resin
3 can be stored at room temperature for a long time without
Table 1 Yields of oxazolidin-2-ones
Entry
R1
R2
Product
Yield/%a
1
2
3
4
5
6
7
8
H
C6H5
7a
7b
7c
7d
7e
7f
84
85
83
85
82
80
80
75
H
C6H5CH2
C6H5OCH2
C6H5CH2OCH2
4-CH3C6H4OCH2
CH3
H
H
H
H
H
C2H5
7g
7h
(CH2)4
aOverall isolated yield based on polymer-supported selenium
bromide (1.18 mmol Br/g).
diminution of capacity or the liberation of disagreeable
odours. With the resin 3 to hand, we examined the synthesis
of target compounds 7. First of all, the O-acylation reaction
was investigated starting from 2-hydroxy-2-phenylethyl
selenide resin (3a) with benzoyl isocyanate in THF at room
temperature for 20 h to afford polystyrene-supported phenyl
2-[(benzoylamino)carbonyl]oxy-2-phenylethylselenide(4a)in
93% yield. This was characterised by its IR spectra featuring a
N–H stretch at 3272 and 1515 cm-1, a C=O stretch at 1756 and
1734 cm-1, a C–O–C stretch at 1056 cm-1, and almost complete
disappearance of the hydroxyl absorption. Next, treatment of
resin 4a with an excess of MCPBA in DMF/THF solvent in
the presence of potassium hydrogenphosphate afforded the
corresponding selenone intermediate 5a. Subsequently the
N-benzoyl-5-phenyl-oxazolidin-2-one (6a) was obtained in
88% yield as a result of the displacement of the selenonyl
group by the nitrogen atom of the carbamate. This
intramolecular cyclisation reaction occurred easily because
of the great leaving ability of the selenonyl group. Finally,
N-benzoyl-5-phenyl-oxazolidin-2-one (6a) was hydrolysed
to the corresponding 5-phenyl-oxazolidin-2-one (7a) in 84%
yield by treatment with 4 N HCl at 65°C for 4 h. In fact, after
a series of experiments, we have found it most convenient to
Epoxide
rt
R1
Se
R2
LiBH4
BzNCO
THF, rt
SeBr
SeLi
THF, rt
OH
1
2
3
BzHN
O
MCPBA
K2HPO4
O
O
O
Se
R1
OCONHBz
R2
4N HCl
65 oC
Se
O
O
NBz
R1
O
NH
R1
O
THF/DMF, rt
R1
R2
R2
R2
4
5
6
7
Scheme 1
* Correspondent. E-mail: shengsr@jxnu.edu.cn
PAPER: 07/4397

JOURNAL OF CHEMICAL RESEARCH 2007 75
9.6 Hz, 1H), 4.56 (d, J = 12.1 Hz, 1H), 4.61 (d, J = 12.2 Hz, 1H),
4.85–4.89 (m, 1H), 5.53 (bs, 1H, NH), 7.02–7.08 (m, 2H), 7.31–7.35
(m, 3H); 13C NMR: δ = 41.7, 46.3, 75.1, 78.5, 155.6, 126.7, 128.3,
129.1, 159.5. IR (KBr): ν = 3286, 1738 cm-1; EIMS: m/z (%) = 207
(M+); Anal. Calcd for C11H13NO3: C, 63.76; H, 6.32; N, 6.76. Found:
C, 63.79; H, 6.38; N, 6.80.
carry out successively the three-step reaction in one-pot from
resin 3a as starting material giving 7a almost in the same yield
without further isolation of selenide resin 4a and 6a. With our
successful initial studies of the preparation of 7a, extension of
this method to the synthesis of other analogues in moderate
to good yields was investigated (Table 1). The residual resin,
polystyrene-supported phenylseleninic acid, was obtained as
a by-product. Its IR spectrum was identical to the previously
reported data.9 The polystyrene-supported phenylseleninic
acid could be converted to polymer-supported selenium
lithium for recycling by treatment with KI/Na2S2O310 followed
by LiBH4. For example, 5-phenyl-oxazolidin-2-one (7a) was
obtained in 80% yield under the same reaction conditions
using the recovered selenium lithium resin (second run), and
in 75% yield after second recycle (i.e. third run). It was shown
that recycling 2–3 times led to a gradual deterioration of the
resin.
5-(4-Methylphenoxymethyl)-oxazolidin-2-one (7e): Colourless oil;
1H NMR: δ = 2.31 (s, 3H), 3.34 (ddd, J = 0.8, 7.1, 8.6 Hz, 1H), 3.62
(ddd, J = 0.8, 8.2, 8.5 Hz, 1H), 3.90 (dd, J = 5.1, 9.7 Hz, 1H), 3.95
(dd, J = 5.2, 9.7 Hz, 1H), 4.85–4.93 (m, 1H), 5.52 (bs, 1H, NH), 7.52
(d, J = 8.5 Hz, 2H), 6.77 (d, J = 8.5 Hz, 2H); 13C NMR: δ = 20.4, 46.5,
76.8, 76.1, 114.5, 121.2, 129.2, 133.6, 160.2; IR (KBr): ν = 3284,
1740 cm-1; EIMS: m/z (%) = 207 (M+); Anal. Calcd for C11H13NO3:
C, 63.76; H, 6.32; N, 6.76. Found: C, 63.78; H, 6.38; N, 6.81.
5-Methyloxazolidin-2-one (7f): Colourless oil (Lit.5b Oil); 1H NMR:
δ = 1.46 (d, J = 6.2 Hz, 3H), 3.21 (ddd, J = 0.8, 7.2, 8.4 Hz, 1H), 3.69
(ddd, J = 0.8, 8.4, 8.4 Hz, 1H), 4.74–4.82 (m, 1H), 5.57 (bs, 1H, NH);
IR (neat): ν = 3298, 1739 cm-1.
5-Ethyl-oxazolidin-2-one (7g): White solid; m.p. 51–52°C (Lit.5c
1
m.p. 51–53°C); H NMR: δ = 1.02 (t, J = 7.5 Hz, 3H), 1.66–1.85
In summary, a novel, convenient, environmentally friendly,
one-pot solid-phase traceless synthesis of oxazolidin-2-
ones in moderate to good yield from polymer-supported
2-hydroxyalkyl selenide by ester-oxidation/cyclisation-
hydrolysis procedure has been developed. This methodology
is applicable for the construction to combinatorial libraries of
oxazolidin-2-ones.
(m, 2H), 3.24 (ddd, J = 1.2, 7.2, 8.4 Hz, 1H), 3.66 (ddd, J = 1.2,
8.4, 8.4 Hz, 1H), 4.56–4.62 (m, 1H), 5.32 (bs, 1H, NH); IR (KBr):
ν = 3299, 1740 cm-1.
Cis-Cyclohexano[b]-2-oxazolidone(7h):Whitesolid;m.p.55–56°C
1
(Lit.11 m.p. 55°C); H NMR: δ = 1.15–1.46 (m, 4H), 1.60–1.84 (m,
2H), 2.10–2.20 (m, 2H), 3.47 (ddt, J = 0.8, 7.5, 8.2 Hz, 1H), 4.72–
4.80 (m, 1H), 5.37 (bs, 1H, NH); IR (KBr): ν = 3281, 1740 cm-1.
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (No. 20562005) and NSF
of Jiangxi Province (No. 0620021).
Experimental
1H NMR spectra were recorded on a Bruker Avance (400 MHz)
spectrometer, using CDCl3 as the solvent and TMS as internal
standard. FT-IR spectra were taken on a Perkin-Elmer SP One FT-
IR spectrophotometer. Mass spectra (EI, 70eV) were recorded on a
HP5989B mass spectrometer. Microanalyses were performed with
a PE 2400 elemental analyser. THF was distilled under N2 from
sodium/benzophenone immediately prior to use. DMF was refluxed
with calcium hydride and distilled under reduced pressure, then
dried over molecular sieves 4Å. Other reagents were obtained from
commercial suppliers and used without further purification.
Received 6 January 2007; accepted 29 January 2007
Paper 07/4397
doi:10.3184/030823407X198267
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5-Phenyl-oxazolidin-2-one (7a): White solid; m.p. 91–92°C (Lit.5b
m.p. 90–91°C); 1H NMR: δ = 3.55 (ddd, J = 0.8, 7.6, 8.6 Hz, 1H), 3.98
(ddd, J = 0.8, 8.6, 8.6 Hz, 1H), 5.50 (bs, 1H, NH), 5.63 (t, J = 8.6 Hz, 1H),
7.34-7.36 (m, 3H), 7.41–7.44 (m, 2H); IR (KBr): ν = 3278, 1721 cm-1.
5-Benzyl-oxazolidin-2-one (7b): White solid; m.p. 108–109°C (Lit.5c
m.p. 107–109°C); 1H NMR: δ = 2.94 (dd, J = 6.8, 14.0 Hz, 1H), 3.15
(dd, J = 6.0, 14.0 Hz, 1H), 3.33 (ddd, J = 0.8, 7.2, 8.4 Hz, 1H), 3.58
(ddd, J = 0.8, 8.4, 8.4 Hz, 1H), 4.83–4.90 (m, 1H), 5.59 (bs, 1H, NH),
7.19–7.23 (m, 3H), 7.32–7.36 (m, 2H); IR (KBr): ν = 3286, 1730 cm-1.
5-(Phenoxymethyl)-oxazolidin-2-one (7c): Colourless oil; 1H NMR:
δ = 3.35 (ddd, J = 0.8, 7.0, 8.5 Hz, 1H), 3.62 (ddd, J = 0.8, 8.5,
8.4 Hz, 1H), 3.90 (dd, J = 9.6, 4.8 Hz, 1H), 3.95 (dd, J = 9.6, 5.2 Hz,
1H), 4.83–4.90 (m, 1H), 5.45 (bs, 1H, NH), 6.96–7.01 (m, 2H), 7.26–
7.29 (m, 3H); 13C NMR: δ = 46.4, 75.0, 76.1, 115.2, 121.7, 129.4,
135.1, 160.1; IR (KBr): ν = 3283, 1736 cm-1; EIMS: m/z (%) = 193
(M+); Anal. Calcd for C10H11NO3: C, 62.17; H, 5.74; N, 7.25. Found:
C, 62.23; H, 5.80; N, 7.31.
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5-(Benzyloxymethyl)-oxazolidin-2-one (7d): Colourless oil; 1H
NMR: δ = 3.33 (ddd, J = 0.8, 7.0, 8.4 Hz, 1H), 3.61 (ddd, J = 0.8,
8.3, 8.1 Hz, 1H), 3.89 (dd, J = 4.8, 9.6 Hz, 1H), 3.93 (dd, J = 5.2,
PAPER: 07/4397