Synthesis of isomeric 2-oxazolidinones from (1R,2R)-and (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediols

Article abstract of DOI:10.1007/s10593-007-0201-z

A synthesis is reported for (4R,5R)-and (4S,5S)-4-hydroxymethyl-5-(4- nitrophenyl)oxazolidin-2-ones and (1′R,4R)-and (1′S,4S)-4- [hydroxy(4-nitrophenyl)methyl]oxazolidin-2-ones from (1R,2R)-and (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediols. The effect of the experimental conditions on the formation of these compounds was studied.

Full text of DOI:10.1007/s10593-007-0201-z

Chemistry of Heterocyclic Compounds, Vol. 43, No. 10, 2007
SYNTHESIS OF ISOMERIC 2-OXAZOLIDI-
NONES FROM (1R,2R)- AND (1S,2S)-2-AMINO-
1-(4-NITROPHENYL)-1,3-PROPANEDIOLS
M. Madesclaire1, V. P. Zaitsev2, J. V. Zaitseva2, and S. Kh. Sharipova2
A synthesis is reported for (4R,5R)- and (4S,5S)-4-hydroxymethyl-5-(4-nitrophenyl)oxazolidin-2-ones and
(1'R,4R)- and (1'S,4S)-4-[hydroxy(4-nitrophenyl)methyl]oxazolidin-2-ones from (1R,2R)- and (1S,2S)-
2-amino-1-(4-nitrophenyl)-1,3-propanediols. The effect of the experimental conditions on the formation
of these compounds was studied.
Keywords: (1R,2R)- and (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediols, (4R,5R)- and (4S,5S)-
4-hydroxymethyl-5-(4-nitrophenyl)oxazolidin-2-ones, (1'R,4R)- and (1'S,4S)-4-[hydroxy(4-nitrophenyl)-
methyl]oxazolidin-2-ones.
2-Oxazolidinones have attracted considerable attention in chemistry. These compounds display a variety
of biological activity [1-4] and are used in asymmetric synthesis [5]. Formation of the 2-oxazolidinone ring is
used when necessary to protect both the adjacent amino and hydroxy groups [6-8].
In our previous work [9], we synthesized (1S,2S)-2-ethoxycarbonylamino-1-(4-nitrophenyl)-
1,3-propanediol (2) from (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediole (1) with subsequent conversion to
isomeric 2-oxazolidinones: (1'S,4S)-4-[hydroxy(4-nitrophenyl)methyl)oxazolidin-2-one (4) and (4S,5S)-
4-hydroxymethyl-5-(4-nitrophenyl)oxazolidin-2-one (3) according to Scheme 1.
It is known that the closure of the oxazolidinone ring upon treatment of a suitable methylcarbamate
proceeds rather rapidly even at room temperature and in a slightly basic medium (pH 9.5) in only 20 min [8]. But
we maintained the reaction mixture under similar conditions for about 120 h, and only a slight amount of
oxazolidinone 4 was obtained as a precipitate [9].
In this conection the aim of the present work was the search of the conditions most favorable for
formation of the one of the isomeric 2-oxazolidinones, permitting a reduction of the reaction time.
Base is a catalyst in the formation of 2-oxazolidinones but it may lead to undesired racemization.
Propanediol 2 is sensitive to the pH value and the solution at pH > 10 turns reddish; the product isolated is less
pure. Thus, propanediol 2 is initially [9] treated with a 1:1 mixture of water and saturated methanolic potassium
carbonate, which has pH ~9.5.
In a search for optimal reaction conditions, the pH of the reaction solution was raised to 10 by addition
solid potassium hydroxide. Furthermore, different amounts of propanediol 2 were treated with equal volumes of
the indicated solution. In experiment 5, 20 ml water was added to 50 ml used solution to reduce the solubility of
oxazolidinone 4 (Table 1).
__________________________________________________________________________________________
1Université
michel.madesclaire@u-clermont.fr.
d’Auvergne,
Faculté
de
State
Farmacie,
Clermont-Ferrand,
443011 Samara,
France;
Russia;
e-mail:
e-mail:
2Samara
University,
vzaitsev@ssu.samara.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1562-1570,
October, 2007. Original article submitted March 2, 2007.
0009-3122/07/4310-1325©2007 Springer Science+Business Media, Inc.
1325

Sheme 1
-4
C6H4NO2
C6H4NO
2 -4
EtOCOCl
HOCHCHCH2OH
NHCOOEt
HOCHCHCH2OH
NH2
2
1
K2CO3
ν1
ν2
ν1 >
ν2
-4
4-
C6H4NO2
O2NH4C6
CH2OH
NH
HOCH
O
O
HN
O
3
O
4
The slight increase in the pH from 9.5 to 10 leads to a significant increase in the reaction rate. The
formation of a precipitate of oxazolidinone 4 in experiments 2-5 starts in the first day. In experiment 1, a
precipitate of oxazolidinone 4 did not separate out upon completion of the reaction, while in experiment 5, the
rapid crystallization of both 3 and 4 occurred after 29 h throughout the entire bulk of the reaction mixture, such
that the reaction was not completed. We should note that in all experiments 1-5, the reaction mixture contained a
slight amount of propanediol 2 after completion of the reaction, as indicated by thin-layer chromatography.
The solubility of oxazolidinone 4 was found to be higher in alkaline medium and thus the reaction
mixtures were subsequently treated as follows. In experiments 1-4, concentrated hydrochloric acid was added
dropwise with stirring to bring the solution pH to 7-8 and mixtures were left overnight for the complete
crystallization of oxazolidinone 4. A precipitate of product 4 also formed in the reaction mixture in experiment 1
after standing overnight (Table 1). A sample of the reaction mixture was taken with a pipette upon rapid stirring
to insure homogeneity. Methanol and water were removed on a rotary evaporator at room temperature, the residue
1
was dried and the ratio of oxazolidinones 3 and 4 was determined on the basis of the H NMR spectra taken in
DMSO-d6 (Table 1). In experiments 1-4, the precipitate of oxazolidinone 4 was filtered off, washed with a small
amount of 1:1 water–methanol, dried, and weighed (Table 1).
TABLE 1. Experimental Data on the Conversion of Propanediol 2 Into
a Mixture of Oxazolidinones 3 and 4 at pH 10
Amount
of compound 2, g
Volume,
ml
Precipitate
mass, g
Reaction time,
h
Experiment
3 : 4, %
1
2
3
4
5
2
4
50
50
50
50
70
0.14
0.50
2.25
4.37
5.50
8
69 : 31
68 : 32
57 : 43
35 : 65
55 : 45
20
28
33
29
8
10
10
1326

In experiment 5, the reaction mixture was treated as follows: a portion of the reaction mixture was
1
removed with a spatula and dried. The ratio of products 3 and 4 was determined by H NMR spectroscopy. The
reaction mixture in this experiment was filtered under vacuum. The precipitate was washed with
1:1 water-methanol, dried, and weighed. The mother liquor was made acidic and combined with the mother
liquors from experiments 1-4. Methanol was then removed on a rotary evaporator at room temperature. The
precipitate formed, which was mainly a mixture of oxazolidinones 3 and 4, was filtered off and dried. This
mixture was used directly for the synthesis of the esters or subjected to chromatography on a silica gel column
using 15:1 ethyl acetate–methanol or ethyl acetate to give additional amounts of 4 and 3.
The reaction course was followed by thin-layer chromatography. The thin-layer chromatography data and
values given in Table 1 showed that oxazolidinone 3 is the product of kinetic control (ν1 > ν2). The concentrations
of 2-4 in solution drop after the begining of precipitation of oxazolidinone 4. A supersaturated solution of 4
apparently forms in the first step of the reaction. Thus, the concentration of this product in solution drops after the
begining of crystallization. The decrease in the concentration of propanediol 2 is related to its conversion to
oxazolidinones 3 and 4, while the decrease in the concentration of oxazolidinone 3 is related to its conversion to
4, which has low solubility and precipitates out. In order to determine whether an equilibrium exists in the
reaction mixture between oxazolidinones 3 and 4 and which of these compounds is the product of thermodynamic
control, solutions of 3 and 4 in the indicated reaction mixture were maintained for 24 h. Both products with the
predominance of oxazolidinone 3 were found after maintenance for 24 h in the solutions, which originally
contained pure oxazolidinone 3 or 4. Thus, oxazolidinone 3 is the product of both kinetic and thermodynamic
control in the conversion of propanediol 2 into oxazolidinones 3 and 4. Equilibrium between products 3 and 4 is
also established upon the treatment of 4 with hydrazine hydrate in ethanol at reflux for 1-2 h though
propanediol 2 is not converted into a mixture of 3 and 4 under these conditions. This failure may be attributed to
the greater acidity of the 2-oxazolidinones and carbamates in comparison with alcohols and permits us to make a
conclusion concerning the mechanism of formation of oxazolidinones 3 and 4, namely, the conversion of
propanediol 2 into oxazolidinones 3 and 4 occurs as an intramolecular nucleophilic replacement of the ethoxy
group.
An alternative mechanism entails the formation of an isocyanate as the result of the loss of an ethoxy
group from the carbamate anion under base catalysis conditions. The alkoxy group is not considered a good
leaving group and such mechanism is considered when there is an aryloxy leaving group [10].
Nevertheless, the existence of an equilibrium between oxazolidinones 3 and 4 and the formation of a
large amount of 4 as a consequence (Table 1) indicate the formation of (1S,2S)-1,3-dihydroxy-1-(4-nitrophenyl)-
2-propyl isocyanate (isocyanate 5) (Scheme 2) from oxazolidinones 3 and 4. Insoluble oxazolidinone 4 (ν4 > ν3),
which separates as a precipitate and, thereby, becomes the major product of this reaction in the step involving the
conversion of isocyanate 5 into a mixture of oxazolidinones 3 and 4, becomes the product of kinetic control.
We attempted to elucidate whether nascent isocyanate 5 reacts with water and methanol (components of
the reaction mixture) to give 1 and 2a, i.e., whether all the reactions shown in Scheme 2 are possible.
The formation of propanediol 2a, whose chromatographic mobility should be virtually identical to the
mobility of 2, might account for the finding that the reaction could not initially be brought to completion.
As already noted, both oxazolidinones 3 and 4, upon suitable treatment, give a mixture of only these
products. An experiment was performed, in which 2 was treated with the indicated water-methanol mixture for
103 h. This experiment terminated with the complete conversion of propanediol 2 and formation of only two
products, oxazolidinones 3 and 4.
Hence, the formation of 1 and 2a is impossible under the reaction conditions.
The experiments carried out both in this work and our previous study [9] indicated that a high yield of 4 is
favored by 1) a higher pH value (~10), 2) prolonged treatment of the reaction mixture, which facilitates the
conversion of 3 to 4, and 3) a minimal volume for the reaction mixture (Table 1, experiment 4), which facilitates
1327

Sheme 2
1
H2O
–CO2
C6H4NO2-4
ν3
ν4
HOCHCHCH2OH
4
3
NCO
5
MeOH
–MeOH
–MeOH
C6H4NO2-4
HOCHCHCH2OH
NHCOOMe
2a
ν4 > ν3
the more complete separation of oxazolidinone 4 as a precipitate. Observing all these conditions permits the
isolation of pure 4 in high yield. On the other hand, a lower pH value (9.5) and larger reaction mixture volume
(Table 1, experiment 1) are more favorable for the formation of oxazolidinone 3. The rapid separation of
oxazolidinone 4 over the course of 24 h is, in our view, undesirable and indicates a pH value over the optimal
value for the preparation of 3. The increase in the pH value probably increases the rate of conversion of 3 to 4 to a
greater extent than the rate of conversion of 2 to the mixture of 3 and 4.
Unfortunately, in contrast to oxazolidinone 4, oxazolidinone 3 could not be isolated from the reaction
mixture as a pure compound.
The pH range from 9.5 to 10 studied in this work is probably close to the limit, below which the reaction
does not proceed. A reduction in the pH during the experiment may be related both to the absorption of
atmospheric carbon dioxide and the presence of impurities.
In light of the data on the reactivity of propanediol 2, (1R,2R)-2-ethoxycarbonylamino-1-(4-nitrophenyl)-
1,3-propanediol (6) was converted to (1'R,4R)-4-[hydroxy(4-nitrophenyl)methyl]oxazolidin-2-one (7) and
(4R,5R)-4-hydroxymethyl-5-(4-nitrophenyl)oxazolidin-2-one (8). Stereoisomers display different biological
activity and, thus, hold interest for biological testing. Esters 9 and 10, which are enantiomers described in our
previous work [9], were obtained from 7 and 8, while two new esters 11 were obtained from 4.
C H
4-O2N
6
4
RCOCH
4-
O2NH4C6
CH2OCR
O
O
O
NH
HN
O
O
O
(4R,5R)
10a-e
9a-e (1'R,4R), 11a, b (1'S,4S)
9, 10 a R = Me, b R = Et, c R= Pr, d R = (CH2)3Cl,e R = PhCHCl;
11 a R = Pr, b R = (CH2)3Cl
1328

We have already noted that the acylation of chromatographically-purified 3 and 4 requires two
equivalents of acid chloride [9]. In the present work, we carried out the acylation of 4, 7, and 8, isolated from the
reaction mixtures and dried in the air. In this case, a total of three or four equivalents of acid chloride was
required for the acylation of these compounds. All the esters obtained are solids and most of them crystallize
readily, especially after purification by column chromatography.
The treatment of oxazolidinones 7 and 8 with the racemic acid chloride of phenylchloroacetic acid gave a
1
mixture of diastereomers. The H NMR spectrum in acetone-d6 showed signals for the protons of the CHCl,
CHAr, and NH groups of both diastereomers of 9e, while the signals of only the protons of the CHCl and CHAr
groups are doubled in the spectrum of the diastereomers of 10e. The diastereomers of 10e are formed in 1:1 ratio,
while the diastereomers of 9e are formed in unequal amounts. The different stereochemical result is readily
attributed to the circumstance that greater steric differences arise in the acylation of the second alcohol group in 7,
which facilitate formation of the diastereomers in unequal amounts, than in the acylation of the first alcohol group
in 8.
EXPERIMENTAL
1
The H NMR spectra were taken on a Bruker Avance 200 spectrometer at 200 MHz in DMSO-d6 or
acetone-d6 with TMS as the internal standard and treated using the MESTREC program. The melting points were
determined on a Koefler block. In the experiments there were used Merck silica plates, silica gel pouwder of SDS
grade, the acid chlorides of Acros, while (1R,2R)- and (1S,2S)-2-amino-4-(4-nitrophenyl)-1,3-propanediols were
supplied by the Akrikhin firm. The chromatographic separation of all the products was carried out on a 3×40 cm
silica gel column using different eluents.
(1S,2S)-2-Ethoxycarbonylamino-1-(4-nitrophenyl)-1,3-propanediol (2). A mixture of 1 (106 g,
0.5 mol), sodium carbonate (106 g, 1 mol), and methylene chloride (600 ml) was added to a 1000-ml
round-bottomed flask equipped with a reflux condenser and magnetic stirrer. Ethyl chlorocarbonate (52.5 ml,
0.53 mol) was added with stirring to the mixture cooled with ice to 5-10°C at a rate such that the temperature did
not rise over 15°C. The reaction mixture was stirred overnight and filtered on a Buchner filter. The precipitate
was washed with methylene chloride. The volume of the filtrate was reduced to 100-150 ml by distilling off
methylene chloride on a water bath. The crystalline precipitate of compound 2 was collected on a Buchner filter
and washed with methylene chloride. The previously obtained precipitate of compound 2 and inorganic
compounds was placed in a beaker and treated with hot ethyl acetate and filtered. This procedure was repeated
two or three times. The organic fractions contain pure 2. These fractions were combined and ethyl acetate was
almost entirely distilled off. The crystalline precipitate was filtered off, washed with a small amount of methylene
chloride, and dried. The two portions of compound 2 were combined. The yield of compound 2 was 112 g (79%);
mp 118°C (mp 118°C [9]).
(1R,2R)-2-Ethoxycarbonylamino-1-(4-nitrophenyl)-1,3-propanediol (6) was obtained analogously in
the reaction of (1R,2R)-2-amino-1-(4-nitrophenyl)-1,3-propanediol (98 g, 0.46 mol) with ethyl chlorocarbonate
(45.5 ml, 0.46 mol) in the presence of sodium carbonate (98 g, 0.92 mol). The yield of 6 was 114 g (87%);
mp 118°C (the mp for the (1S,2S)-stereoisomer was 118°C [9]).
(1'S, 4S)-4-[Hydroxy(4-nitrophenyl)methyl]oxazolidin-2-one (4). A mixture of compound 2 (10 g,
35 mmol), water (50 ml), and saturated methanolic sodium carbonate (50 ml) was added to a 250-ml
round-bottomed flask equipped with a magnetic stirrer. The flask was sealed with a stopper and the reaction
mixture was stirred with the magnetic stirrer. After 67 h, the reaction mixture was brought to pH 7-8 by adding
concentrated hydrochloric acid and left overnight. The precipitate of almost pure compound 4 was filtered off.
The yield of compound 4 was 5.67 g (68%); mp 205-206 (mp 206-207°C [9]).
1329

(4S,5S)-4-Hydroxymethyl-5-(4-nitrophenyl)oxazolidin-2-one (3). Methanol was removed from the
mother liquor obtained in the previous experiment on a rotary evaporator. A crystalline precipitate formed, which
was filtered off, washed with water, and dried. The isolated product (2.07 g, 25.7%) was a mixture of 3 and 4 with
predominance of the former. Oxazolidinone 3 was purified by chromatography on a silica gel column with
15:1 ethyl acetate–methanol as the eluent and recrystallized from ethyl acetate, mp 136-137°C (mp 137-138°C [9]).
(1'R,4R)-4-[Hydroxy(4-nitrophenyl)methyl]oxazolidin-2-one (7) was obtained analogously by treating
compound 6 (12 g, 42 mmol) with the indicated aqueous methanolic sodium carbonate solution (90 ml) for 54 h.
The yield of 7 was 4.4 g (44%); mp 206-207°C (mp for the (1'S, 4S)-stereoismer 206-207°C [9]).
(4R,5R)-4-Hydroxymethyl-5-(4-nitrophenyl)oxazolidin-2-one (8). A mixture of 7 and 8 was isolated
from the mother liquor obtained in the previous experiment (3.27 g, 33%). Oxazolidinone 8 was purified by
column chromatography using 15:1 ethyl acetate–methanol as the eluent and recrystallized from ethyl acetate,
mp 136-137°C (mp for the (4S,5S)-stereoisomer 137-138°C [9]).
(1'R,4R)-4-[Butanoyloxy(4-nitrophenyl)methyl]oxazolidin-2-one (9c). A mixture of compound 7
(1.5 g, 6.3 mmol), chloroform (25 ml), and pyridine (5.5 ml, 68 mmol) was added to a 100 ml round-bottomed
flask equipped with a magnetic stirrer. Then, butanoyl chloride (2.68 g, 25.2 mmol) was slowly added dropwise
with stirring. The mixture was stirred for 1 h. Then, water (15 ml) was added and the mixture was stirred for an
additional 1 h. The reaction mixture was transferred to a separatory funnel and chloroform (30 ml) was added.
The organic layer was separated, washed with dilute hydrohloric acid, aqueous sodium bicarbonate, and water,
and dried over sodium sulfate. Chloroform was distilled off and the dry product was purified by chromatography
on a silica gel column using 7:3 ethyl acetate-methanol as the eluent. The solvent was distilled off on a rotary
evaporator and the crystalline precipitate was washed on the filter with 1:1 ethyl acetate–methanol. The yield of
1
9c was 1.50 g (77%); mp 118-119°C. H NMR spectrum (acetone-d6), δ, ppm (J, Hz): 7.73-8.30 (4H,
H arom); 7.09 (1H, br. s, NH), 5.97 (1H, d, J = 5.4, CH–O); 4.22-4.45 (3H, m, CH–N and CH2–O); 2.47 (2H,
t, J = 6.5, CH2–CO); 1.65 (2H, m, CH2); 0.92 (3H, t, J = 7.3, CH3). Found, %: C 55.03; H 5.26; N 9.30.
C14H16N2O6. Calculated, %: C 54.54; H 5.23; N 9.09.
(1'S,4S)-4-[Butanoyloxy(4-nitrophenyl)methyl]oxazolidin-2-one (11a) was obtained analogously by
the reaction of compound 4 (3 g, 12.6 mmol) and butanoyl chloride (4.02 g, 37.8 mmol). The yield of 11a was
2.8 g (72%); mp 118-119°C.
(1'R,4R)-4-[4-Chlorobutanoyloxymethyl-(4-nitrophenyl)]oxazolidin-2-one (9d)
was obtained
analogously by the reaction of compound 7 (1.5 g, 6.3 mmol) and 4-chlorobutanoyl chloride (3.55 g,
25.2 mmol). The crude product was purified chromatographically using 5:2 ethyl acetate–cyclohexane as the
1
eluent. The yield of 9d was 1.84 g (77%); mp 122-123°C. H NMR spectrum in acetone-d6, δ, ppm (J, Hz):
7.76-8.30 (4H, H arom); 7.14 (1H, br. s, NH); 5.98 (1H, d, J = 5.8, CH–O); 4.23-4.44 (3H, m, CH–N and CH2–O);
3.66 (2H, t, J = 6.4, CH2Cl); 2.66-2.74 (2H, m, CH2); 2.04-2.16 (2H, CH2CO; overlaps with the signal for
acetone-d6), Found, %: C 49.54; H 4.47; Cl 10.34; N 8.21. C14H15ClN2O6. Calculated, %: C 49.06; H 4.41;
Cl 10.34; N 8.17.
(1'S,4S)-4-[4-Chlorobutanoyloxymethyl-(4-nitrophenyl)]oxazolidin-2-one (11b) was obtained
analogously by the reaction of compound 4 (3 g, 12.6 mmol) and 4-chlorobutanoyl chloride (5.33 g, 37.8 mmol).
The yield of 11b was 2.77 g (64%); mp 122-123°C.
(1'R,4R)-4-[Acetoxy(4-nitrophenyl)methyl]oxazolidin-2-one (9a) was obtained analogously by the
reaction of compound 7 (2 g, 8.4 mmol) and) acetyl chloride (2.64 g, 33.6 mmol). The crude product was purified
chromatographically using 5:2 ethyl acetate–cyclohexane as the eluent. The yield of 9a was 1.92 g (82%);
mp 175-176°C (mp for the (1'S,4S)-stereoisomer was 156°C [9]).
(1'R,4R)-4-[(4-Nitrophenyl)propionyloxymethyl]oxazolidin-2-one (9b) was obtained analogously by
the reaction of compound 7b (1.5 g, 6.3 mmol) and propionyl chloride (2.33 g, 25.2 mmol). The crude product
was purified chromatographically using 5:2 ethyl acetate–cyclohexane as the eluent. The yield of 9b was 1.47 g
(79%); mp 147-148°C (mp for the (1'S,4S)-stereoisomer 149-150°C [9]).
1330

(1'R,4R)-4-[(4-Nitrophenyl)-(R,S)-phenylchloroacetoxymethyl]oxazolidin-2-one (9e) was obtained
analogously by the reaction of compound 7 (1.5 g, 6.3 mmol) and propionyl chloride (3.6 g, 19.0 mmol). The
crude product was purified chromatographically using 5:2 ethyl acetate–cyclohexane as the eluent. The yield of
9e was 1.43 g (58%); mp 72-73°C (mp for the (1'S,4S)-stereoisomer 72-73°C [9]).
(4R,5R)-4-Acetoxymethyl-5-(4-nitrophenyl)oxazolidin-2-one (10a) was obtained analogously by the
reaction of mixture of the compounds 7 and 8 (2.1 g, 8.8 mmol) and acetyl chloride (2.08 g, 26.5 mmol). The
crude product was purified by chromatography using 5:2 ethyl acetate–cyclohexane as the eluent. The yield of
10a was 1.45 g (59%); mp 68°C (mp for the (4S,5S)-stereoisomer 68°C [9]).
(4R,5R)-5-(4-Nitrophenyl)-4-propionyloxymethyl-2-oxazolidinone (10b) was obtained analogously by
the reaction of mixture of the compounds 7 and 8 (2 g, 8.4 mmol) and propionyl chloride (2.33 g, 25.2 mmol).
The crude product was purified chromatographically using 7:3 ethyl acetate-cyclohexane as the eluent. The yield
of 10b was 1.47 g (60%); mp 105°C (mp for the (4S,5S)-stereoisomer 105°C [9]).
(4R,5R)-4-Butanoyloxymethyl-5-(4-nitrophenyl)oxazolidin-2-one (10c) was obtained analogously by
the reaction of mixture of the compounds 7 and 8 (2 g, 8.4 mmol) and butanoyl chloride (2.68 g, 25.2 mmol).
The crude product was purified chromatographically using 6:4 ethyl acetate–cyclohexane as the eluent. The yield
of 10c was 1.65 g (57%); mp 101-102°C (mp for the (4S,5S)-stereoisomer 100-101°C [9]).
(4R,5R)-4-(Chlorobutanoyloxymethyl)-5-(4-nitrophenyl)oxazolidin-2-one (10d) was obtained
analogously by the reaction of mixture of the compounds 7 and 8 (2 g, 8.4 mmol) and 4-chlorobutanoyl chloride
(3.55 g, 25.2 mmol). The crude product was purified chromatographically using 6:4 ethyl acetate–cyclohexane as
the eluent. The yield of 10d was 0.91 g (57.1%); mp 128-129°C (mp for the (4R,5R)-stereoisomer
129-130°C [9]).
(4R,5R)-5-(4-Nitrophenyl)-(R,S)-4-(phenylchloroacetoxymethyl)oxazolidin-2-one (10e) was obtained
analogously by the reaction of mixture of the compounds 7 and 8 (2 g, 8.4 mmol) and racemic
phenylchloroacetyl chloride (4.76 g, 25.2 mmol). The crude product was purified chromatographically using 1:1
ethyl acetate–cyclohexane as the eluent. The yield of 10e was 1.88 g (57%); mp 132-133°C (mp for the
(4S,5S)-stereoisomer 132-133°C [9]).
Experiments on the Isomerization of 2-Oxazolidinones 3 and 4.
1. A sample of chromatographically pure compound 4 (0.15 g) and 1:1 mixture of distilled water and
saturated methanolic potassium carbonate (15 ml) were added to a 50-ml round-bottomed flask equipped with a
magnetic stirrer. The flask was sealed and left over night. Thin-layer chromatography using ethyl acetate as the
eluent showed presence of 3 and 4 with the predominance of 3.
2. A sample of chromatographically pure compound 4 (0.238 g, 1 mmol) and hydrazine hydrate (0.5 g,
10 mmol) in ethanol (15 ml) were added to a 50-ml round-bottomed flask. The mixture was heated at reflux for
2 h. Thin-layer chromatography with ethyl acetate as the eluent showed the presence of 3 and 4 with the
predominance of 3.
Similar results were obtained in the isomerization of oxazolidinone 3.
The authors express their gratitude to Leal Fernand for assistance in this work and participating in a
discussion of the results.
REFERENCES
1.
2.
R. C. Thomas, Toni-Jo. Poel, and M. R. Barbachyn, US Patent 5968962; Ref. Zh. Khim., 19O, 129P
(2001).
S. Bartel, S. Raddatz, M. Hanter, U. Rosentreter, H. Wild, R. Endermann, and H. P. Kroll, Eur. Pat.
Appl. 1029854; Ref. Zh. Khim., 19O, 132P (2001).
1331

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