5-(α-Halobenzyl)- and 5-Benzylidene-2,2-dimethyl-1,3-oxazolidin-4-ones in Synthesis of α-Hydroxy Acids

Article abstract of DOI:10.1134/S1070363217120088

The reactions of acid hydrolysis of 5-(α-halobenzyl)- and 5-benzylidene-2,2-dimethyl-1,3-oxazolidin-4-ones were studied. A possibility of the synthesis of corresponding α-hydroxy acids was shown.

Full text of DOI:10.1134/S1070363217120088

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 12, pp. 2801–2809. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © V.A. Mamedov, V.L. Mamedova, G.Z. Khikmatova, D.E. Korshin, O.G. Sinyashin, 2017, published in Zhurnal Obshchei Khimii,
2017, Vol. 87, No. 12, pp. 1984–1992.
Dedicated to B.I. Buzykin on His 80th Anniversary
5-(α-Halobenzyl)-
and 5-Benzylidene-2,2-dimethyl-1,3-oxazolidin-4-ones
in Synthesis of α-Hydroxy Acids
V. A. Mamedova,b*, V. L. Mamedovaa,b, G. Z. Khikmatovaa,b,
D. E. Korshina,b, and O. G. Sinyashina,b
a Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences,
ul. Akademika Arbuzova 8, Kazan, Tatarstan, 420088 Russia
*e-mail: mamedov@iopc.ru
b Kazan State Technological University, Kazan, Tatarstan, Russia
Received June 1, 2017
Abstract―The reactions of acid hydrolysis of 5-(α-halobenzyl)- and 5-benzylidene-2,2-dimethyl-1,3-oxazolidin-
4-ones were studied. A possibility of the synthesis of corresponding α-hydroxy acids was shown.
Keywords: 5-(halobenzyl)-2,2-dimethyl-1,3-oxazolidin-4-ones, 5-benzylidene-2,2-dimethyl-1,3-oxazolidin-4-
ones, 3-halo-2-hydroxy-3-arylpropionic acids, 2-hydroxy-3-arylacrylic acids, stereoselectivity
DOI: 10.1134/S1070363217120088
α-Hydroxy- and α-oxo acids are widely used in
synthetic organic chemistry [1–5]. Many of them are
biologically active substances widely used as building
blocks for the production of other biologically active
compounds [4–6].
ketenes were used for the formation of 5-substituted
oxazolidine ring by reacting with N-acylsulfylimines
[19, 20] or oxaziridines [8]. In addition to these
methods, we have previously developed a convenient
approach to the preparation of 5-(α-halobenzyl)- and
5-benzylidene-2,2-dimethyl-1,3-oxazolidin-4-ones from
3-aryl-2,3-epoxypropionic acid amides [21]. The latter
were obtained from commercially available α-chloro-
acetamide and aromatic aldehydes by the Darzens con-
densation. Here we report on a stereo- and regio-
selective synthesis of α-hydroxy acids based on 5-(α-
halobenzyl)- and 5-benzylidene-2,2-dimethyl-1,3-oxazol-
idin-4-ones.
Interest in α-hydroxy compounds grew due to the
development of the asymmetric synthesis methods [3,
6–9]. However, there is a restricted number of
approaches to the preparation of these compounds [7–
10]. The diversity of α-hydroxy acids is limited by the
availability of starting materials for their preparation
by the known methods. A possibility of preparing
α-hydroxy acids by acid hydrolysis of 1,3-oxazolidin-
2-ones have been shown in [9, 11, 12]. The variety of
α-hydroxy acids obtained by this method is determined
by the substituents in the position 5 of the oxazol-
idinone ring. General methods of the oxazolidinones
synthesis [13–17] are based on the use of α-hydroxy
acids and their derivatives, therefore obtaining new
α-hydroxy acids from them requires the modification
of substituents in the position 5 [9, 17, 18]. Only
2 methods were published describing the formation of
5-substituted 1,3-oxazolidin-2-one skeleton without
the involvement of α-hydroxy acids. In both methods
Synthesis of 5-(halobenzyl)-2,2-dimethyl-1,3-oxa-
zolidin-4-ones is shown in Scheme 1. 3-Aryl-2,3-epoxy-
propionic acid amides 1 can be prepared as cis- and
trans-isomers while oxazolidinones 2 having 2 chiral
centers can be formed as two diastereomers. As it was
shown in [21], trans-epoxy compounds 1 were selec-
tively obtained when using benzaldehydes bearing
electron-withdrawing groups, whereas reaction with
hydrobromic acid in acetone afforded only syn-5-(α-
bromobenzyl)oxazolidinones 2.
2801

2802
MAMEDOV et al.
Scheme 1.
O
3
NH
O
O
4
O
acetone, HHlg
NaOMe, MeOH
O
Ar
Ar
Ar
Hlg
5
Cl
+
NH2
NH2
20оС, 5 h
20оС, 24 h
2
O1
1
2
Scheme 2.
Cl
O
O
H
O
H
NH2
NH2
HCl, dioxane
20оС, 20 min
HCl, Δ, 1 h
OH
syn-3a, 3b
R
R
trans-1a, 1b
acetone,
H2SO4, 20оС, 24 h
HCl, Δ,
15 min
O
NH
O
Cl
H
HCl, acetone,
20оС, 24 h
H
R
syn-2a, 2b
HCl, Δ, 1 h
Cl
O
HCl, Δ, 2 h
OH
OH
R
syn-4a, 4b
R = 4-NO2 (a), 2-CF3 (b).
In this work, we prepared syn-diastereomers of the
corresponding 5-(α-chlorobenzyl)oxazolidin-4-ones 2
by reacting hydrochloric acid with trans-3-(4-
nitrophenyl)- (1a) and trans-3-[2-(trifluoromethyl)
phenyl]-2,3-epoxypropionic (1b) acids amides in
acetone solution. Compounds 2a and 2b were
subjected to boiling in concentrated hydrochloric acid
for 15 minutes and 1 hour. After short-term boiling,
the corresponding amides of 3-chloro-2-hydroxy-3-
arylpropionic acids 3a and 3b were isolated; prolonged
boiling resulted in acids 4a and 4b. In addition, 3-
chloro-2-hydroxy-3-arylpropionic acid amides 3a and
3b, oxazolidinone precursors formed by the action of
hydrochloric acid on dioxane solutions of the cor-
responding epoxy compounds, were subjected to acid
hydrolysis, as well as epoxy compounds 1a and 1b.
The acid hydrolysis of compounds 1 and 3 resulted in
the formation of α-hydroxy acids 4a and 4b. In [9, 11,
12] it was reported that in the case of oxazolidinones
hydrolysis the configuration of the C5 atom is retained.
In our case, the hydrolysis of oxazolidinones 2
proceeded diastereoselectively to produce the same
diastereomer as in the hydrolysis of epoxy compound
1 or its hydrochlorinated product 2: obviously, the syn-
diastereomer is formed (Scheme 2).
It should be noted that not so many methods for the
preparation of 3-halo-2-hydroxy-3-arylpropionic acids
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5-(α-HALOBENZYL)- AND 5-BENZYLIDENE-2,2-DIMETHYL-1,3-OXAZOLIDIN-4-ONES
2803
Scheme 3.
O
Cl
O
NH
Cl
H
OEt
HCl, EtOH, Δ, 1 h
O
H
OH
CF3
CF3
syn-2b
syn-4b'
Scheme 4.
O
Cl
O
H
O
H
K2CO3, MeOH
OH
OH
OH
syn-4a
O2N
O2N
trans-5a
have been reported, and the variety of the acids
obtained by these methods is small. Cinnamic [22, 23]
or phenylglycidic [24] acids are mainly modified, the
latter being obtained from cinnamic acid esters [23].
5-Benzylidene-2,2-dimethyl-1,3-oxazolidin-4-ones
7 were prepared similarly to the procedure described in
[21] (Scheme 7). They were hydrolyzed with boiling
concentrated hydrochloric acid for 15 minutes,
resulting in the formation of 2-hydroxy-3-arylacrylic
acids 6 (Scheme 8). Moreover, irrespective of whether
cis- or trans-isomer of 7 was hydrolyzed, the same
regioisomer 6 was isolated. This can be due to the
existence of a tautomeric equilibrium between the enol
and ketone forms of 6, which was completely
displaced towards the enol form when recording the
NMR spectra (Scheme 9). In [29–31] the cis-structure
was ascribed to the enol form.
Compound 2b was hydrolysed with hydrochloric
acid in ethyl alcohol. 3-Chloro-2-hydroxy-3-[2-(tri-
fluoromethyl)phenyl]propionic acid ethyl ester was
isolated from the reaction mixture (Scheme 3).
The reaction of compound 4a treated with K2CO3 in
MeOH furnished 3-(4-nitrophenyl)glycidic acid 5 as a
single regioisomer (Scheme 4). The published data on
similar transformations [22, 25], as well as the com-
parison of the 1H NMR spectrum of compound 5a with
the spectra of the previously studied epoxy compounds
[26, 27] made it possible to assign transoid structure to
this isomer.
2-Hydroxyacrylic acids (α-oxo acids) are of
considerable interest for synthetics due to important
role in biological processes, such as biosynthesis and
metabolism of amino acids [29]. Interest in the
synthesis of α-oxo acids remains since pyruvic acid
has been discovered by Berzelius in 1835 [32].
Another reaction outcome was observed in the case
of hydrolysis with hydrochloric acid under reflux for
1 h of oxazolidinones bearing chlorine or bromine in
the benzene ring or with no substituent which were
obtained stereoselectively from the syn- or anti-dia-
stereomers of the corresponding amides 3 [21]
(Scheme 5).
Aromatic α-oxo acids are most often obtained by
the acid hydrolysis of 4-benzylideneoxazol-5-ones
synthesized by the reaction of N-acetylglycine with
aldehydes in the presence of sodium acetate in boiling
acetic acid [33–38]. A newer method [29] involves the
hydrolysis of glycine-based 1-acetyl-3-benzylidene-
piperazine-2,5-diones. Self-condensation of glycine
results in piperazine-2,5-diones. The latter are acylated
with acetic anhydride in DMF, and the acylation
products react with aldehydes in the presence of
t-BuOK to form 1-acetyl-3-benzylidenepiperazine-2,5-
diones subjected to hydrolysis. Here another method
1
The H NMR spectra indicated the formation of
2-hydroxy-3-arylacrylic acids 6 in one regioisomeric
form, regardless of which stereoisomeric (syn- or anti-)
oxazolidinone (for example, compound 2c) was hydro-
lyzed. Apparently, the hydrolysis process was accom-
panied with the dehydrohalogenation of intermediate
3-halo-2-hydroxy-3-arylpropionic acids (Scheme 6).
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2804
MAMEDOV et al.
Scheme 5.
O
H
O
NH2
H
R
trans-1c_1e
HX, dioxane, 20oC, 1 h
X
O
X
O
NH2
NH2
OH
anti-3c
OH
syn-3c_3e
R
R
acetone, H2SO4,
20οC, 24 h
acetone, H2SO4,
20οC, 24 h
H
O
O
O
NH
NH
H
X
X
HCl, Δ
OH
OH
HCl, Δ
H
R
O
O
R
H
H
R
6c_6e
syn-2c_2e
anti-2c
R = H (c), Br (d), Cl (e); Х = Cl (2c, 2e, 3c, 3e), Br (2c', 2d, 3c', 3d).
Scheme 6.
O
Ar
O
O
NH
Ar
Hlg
Ar
O
OH
Hlg
OH
R
O
OH
OH
6
2
Scheme 7.
R
O
NH
NH
K2CO3,
MeOH
O
O
X
2
7
R = 4-NO2, X = Cl (syn-2а); R = 4-CF3, X = Br (syn-2b'); R = H, X = Br (syn-2c', anti-2c'); R = 4-Br, X = Br (syn-2d);
R = 4-Cl, X = Cl (syn-2e); R = 4-NO2 (trans-7а), 4-CF3 (trans-7b), Н (cis-7c, trans-7c), 4-Br (trans-7d), 4-Cl (trans-7e).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 12 2017

5-(α-HALOBENZYL)- AND 5-BENZYLIDENE-2,2-DIMETHYL-1,3-OXAZOLIDIN-4-ONES
2805
Scheme 8.
O
R
NH
O
O
NH
HCl, Δ, 15 min
O
cis-7c
H
OH
HCl, Δ, 15 min
OH
O
R
trans-7a_7e
R
6
R = NO2 (а), CF3 (b), Н (c), Br (d), Cl (e).
Scheme 9.
Ar
O
Ar
O
O
H
O
H
O
Ar
OH
H
OH
H
OH
Ar
OH
Ar
OH
OH
trans
O
O
OH
cis
OH
for the preparation of α-oxo acids by the hydrolysis of
5-benzylidene-1,3-oxazolidin-4-ones was developed
based on commercially available α-chloroacetamide
and aromatic aldehydes.
8.8 Hz), 7.67 br.s (1H, NH), 8.24 d (2H, H3,5Ar, J =
8.8 Hz). Found, %: C 51.99; H 3.83; N 13.52. C9H8N2O4.
Calculated, %: C 51.93; H 3.87; N 13.46.
trans-3-[2-(Trifluoromethyl)phenyl]-2,3-epoxy-
propionic acid amide (trans-1b). Yield 20.58 g
(89%), white solid, mp 209–211°C. IR spectrum, ν, cm–1:
In summary, 3-halo-2-hydroxy-3-arylpropionic and
2-hydroxyaryl-acrylic acids were prepared in good
yields by acid hydrolysis of 5-(halobenzyl)-2,2-di-
methyl-1,3-oxazolidin-4-ones and 5-benzylidene-2,2-
dimethyl-1,3-oxazolidin-4-ones.
1
3361, 3193 (NH2), 1666, 1609 [C(О)NH2]. H NMR
spectrum, δ, ppm: 3.44 d (1H, CH2, J = 1.9 Hz), 4.22
br.s (1H, CH3), 7.45 d (1H, H6Ar, J = 7.7 Hz), 7.52 br.s
(1H, NH), 7.57 d.d (1H, H5Ar, J = 7.6, J = 7.6 Hz), 7.71
d.d (1H, H4Ar, J = 7.6, 7.6 Hz), 7.76 d (1H, H3Ar, J =
7.8 Hz), 7.85 br.s (1H, NH). Found, %: C 51.99; H
3.41; F 24.55; N 6.36. C10H8F3NO2. Calculated, %: C
51.96; H 3.49; F 24.65; N 6.06.
EXPERIMENTAL
Starting materials and solvents were used without
further purification. Melting points were determined
on a Stuart SMP-10 apparatus. IR spectra were recorded
trans-3-(4-Chlorophenyl)-2,3-epoxypropionic acid
amide (trans-1e). Yield 17.58 g (89%), white solid,
mp 164–165°C. IR spectrum, ν, cm–1: 3361, 3176
1
on a Bruker Vector-22 spectrometer in mineral oil. H
NMR spectra were recorded on a Bruker Avance-400
and 600 instruments using DMSO-d6 as a solvent.
1
(NH2), 1666 [C(О)NH2]. H NMR spectrum, δ, ppm:
3.51 d (1H, CH2, J = 1.8 Hz), 4.22 d (1H, CH3, J =
1.8 Hz), 7.37 d (2H, H2,6Ar, J = 8.5 Hz), 7.43 br.s (1H,
NH), 7.44 d (2H, H3,5Ar, J = 8.5 Hz), 7.63 br.s (1H,
NH). Found, %: C 54.63; H 4.01; Cl 17.67; N 7.14.
C9H8ClNO2. Calculated, %: C 54.70; H 4.08; Cl 17.94;
N 7.09.
3-Aryl-2,3-epoxypropionic acid amides 1a–1e
were prepared according to the procedure described in
[21] from 9.35
g (0.10 mol) of commercial
α-chloroacetamide and 0.10 mol of the corresponding
aldehyde under Darzens condensation conditions.
trans-3-(4-Nitrophenyl)-2,3-epoxypropionic acid
amide (trans-1a). Yield 18.95 g (91%), yellow solid,
mp 206–207°C. IR spectrum, ν, cm–1: 3399, 3157
5-(Chlorobenzyl)-2,2-dimethyl-1,3-oxazolidin-4-
ones 2a and 2b were prepared according to the
procedure described in [21] from 0.01 mol of the
corresponding epoxy compound 1, 100 mL of acetone,
and 100 mL of conc. hydrochloric acid.
1
(NH2), 1644, 1602 [C(О)NH2]. H NMR spectrum, δ,
ppm: 3.57 d (1H, CH2, J = 1.8 Hz), 4.26 d (1H, CH3,
J = 1.8 Hz), 7.50 br.s (1H, NH), 7.64 d (2H, H2,6Аr, J =
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 12 2017

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MAMEDOV et al.
syn-5-(α-Chloro-4-nitrobenzyl)-2,2-dimethyl-1,3-
3-Chloro-2-hydroxy-3-arylpropionic acids amides
(3a–3e). a. To 2 mmol of the corresponding 5- (chloro-
benzyl)-2,2-dimethyl-1,3-oxazolidin-4-one 2 was added
3 mL of conc. HCl. The mixture was refluxed for
15 min with stirring, and then poured into water
(25 mL). The precipitate was filtered off, washed with
water, and dried in air.
oxazolidin-4-one (syn-2a). Yield 2.48 g (87%), yellow
solid, mp 228°C. IR spectrum, ν, cm–1: 3231 (NH2),
1721, 1686 [C(О)NH2], 1530 (NO2). 1H NMR
spectrum, δ, ppm: 1.08 s (3H, Ме), 1.34 s (3H, Ме),
4.87 d (1H, CHО, J = 2.8 Hz), 5.58 d (1H, CHCl, J =
2.7 Hz), 7.74 d (2H, H2,6Ar, J = 8.7 Hz), 8.21 d (2H,
H3,5Ar, J = 8.8 Hz), 9.03 s (1H, NH). Found, %: C
50.67; H 4.54; Cl 12.73; N 9.54. C12H13ClN2O4.
Calculated, %: C 50.63; H 4.60; Cl 12.45; N 9.84.
b. The product was prepared according to the
procedure described in [21] from 0.01 mol of the
corresponding epoxy compound 1, 100 mL of dioxane
and 100 mL of conc. hydrochloric acid.
syn-5-[α-Chloro-2-(trifluoromethyl)benzyl]-2,2-
dimethyl-1,3-oxazolidin-4-one (syn-2b). Yield 2.52 g
(82%), white solid, mp 97–98°C. IR spectrum, ν, cm–1:
3180, 3053 (NH2), 1731 [C(О)NH2]. 1H NMR
spectrum, δ, ppm: 1.36 s (3H, Ме), 1.37 s (3H, Ме),
4.87 d (1H, CHO, J = 4.4 Hz), 5.29 d (1H, CHCl, J =
4.4 Hz), 7.55 d.d (1H, H5Ar, J = 7.5, J = 7.6 Hz), 7.71 d
(1H, H6Ph, J = 10.5 Hz), 7.74 d.d (1H, H4Ph, J = 7.5, J =
7.6 Hz), 8.22 d (1H, H3Ar, J = 7.9 Hz), 9.17 s (1H,
NH). Found, %: C 50.63; H 4.21; Cl 29.77; N 4.58.
C13H13ClF3NO2. Calculated, %: C 50.74; H 4.26; Cl
11.52; F 18.52; N 4.55.
syn-3-Chloro-2-hydroxy-3-(4-nitrophenyl)propionic
acid amide (3a) was prepared according to procedure
a. Yield 0.44 g (91%), white solid, mp 206–207°C. IR
spectrum, ν, cm–1: 3482, 3109 (NH2), 1707, 1606
1
[C(О)NH2], 1521 (NO2). H NMR spectrum, δ, ppm:
4.39 d (1H, CH2, J = 4.9 Hz), 5.45 d (1H, CH3, J =
4.9 Hz), 7.23 br.s (1H, NH), 7.33 br.s (1H, NH), 7.69 d
(2H, H2,6Ar, J = 8.8 Hz), 7.42 d (2H, H3,5Ar, J = 8.8 Hz).
Found, %: C 44.35; H 3.77; Cl 14.28; N 11.49.
C9H9ClN2O4. Calculated, %: C 44.19; H 3.71; Cl
14.49; N 11.45.
5-(Chlorobenzyl)-2,2-dimethyl-1,3-oxazolidin-4-
ones 2c and 2e were prepared according to the
procedure described in [21] from 0.01 mol of the
corresponding 3-chloro-2-hydroxy-3-arylpropionic
acid 3, 100 mL of acetone and 7 mL of conc. sulfuric
acid.
syn-3-Chloro-2-hydroxy-3-[2-(trifluoromethyl)-
phenyl]propionic acid amide (3b) was prepared
according to procedure a. Yield 0.47 g (88%), white
solid, mp 150–151°C. IR spectrum, ν, cm–1: 3373,
3186 (NH2), 1687, 1629 [C(О)NH2]. 1H NMR
spectrum, δ, ppm: 4.52 d (1H, CH2, J = 7.5 Hz), 5.45 d
(1H, CH3, J = 7.5 Hz), 7.26 br.s (1H, NH), 7.54 d.d
(1H, H5Ar, J = 7.6, J = 7.6 Hz), 7.60 br.s (1H, NH),
7.71 d (1H, H6Ar, J = 8.2 Hz), 7.73 d.d (1H, H4Ar, J =
8.2, J = 7.6 Hz), 7.97 d (1H, H3Ar, J = 7.9). Found, %:
C 44.66; H 3.43; Hlg 34.49; N 5.28. C10H9ClF3NO2.
Calculated, %: C 44.88; H 3.39; Cl 13.25; F 21.30; N
5.23.
syn-5-(α-Chlorobenzyl)-2,2-dimethyl-1,3-oxazol-
idin-4-one (syn-2c). Yield 1.99 g (83%), white solid,
mp 172–173°C. IR spectrum, ν, cm–1: 3258 (NH2),
1
1715, 1682 [C(О)NH2]. H NMR spectrum, δ, ppm:
1.01 s (3H, Ме), 1.33 s (3H, Ме), 4.80 d (1H, CHО,
J = 2.5 Hz), 5.38 d (1H, CHCl, J = 2.5 Hz), 7.30–7.55
m (4H, H3,4,5Ph), 7.46 d (2H, H2,6 Ph, J = 6.5 Hz), 8.92 s
(1H, NH). Found, %: C 60.53; H 5.81; Cl 14.63; N
5.88. C12H14ClNO2. Calculated, %: C 60.13; H 5.89;
Cl 14.79; N 5.84.
syn-3-Chloro-2-hydroxy-3-phenylpropionic acid
amide (syn-3c) was prepared according to procedure
b. Yield 1.65 g (89%), white solid, mp 151–152°C. IR
spectrum, ν, cm–1: 3380, 3186 (NH2), 1659 [C(О)
NH2]. 1H NMR spectrum, δ, ppm: 4.33 d (1H, CH2, J =
5.3 Hz), 5.28 d (1H, CH3, J = 5.3 Hz), 7.16 br.s (1H,
syn-5-(α-Chloro-4-chlorobenzyl)-2,2-dimethyl-1,3-
oxazolidin-4-one (syn-2e). Yield 2.33 g (85%), a light
yellow solid, mp 173–174°C. IR spectrum, ν, cm–1:
NH), 7.27–7.33 m (4H, NH + H3,4,5Ph), 7.42 d (2H, H2,6
,
Ph
1
3198, 3087 (NH2), 1710 [C(О)NH2]. H NMR spec-
J = 7.9 Hz ). Found, %: C 54.65; H 5.01; Cl 17.69; N
7.08. C9H10ClNO2. Calculated, %: C 54.15; H 5.05; Cl
17.76; N 7.02.
trum, δ, ppm: 1.06 s (3H, Ме), 1.34 s (3H, Ме), 4.79 d
(1H, CHО, J = 2.7 Hz), 5.41 d (1H, CHCl, J = 2.6 Hz),
7.41 d (2H, H2,6Ar, J = 8.6 Hz), 7.48 d (2H, H3,5Ar, J =
8.6 Hz), 8.99 s (1H, NH). Found, %: C 52.63; H 4.58;
Cl 25.54; N 5.18. C12H13Cl2NO2. Calculated, %: C
52.57; H 4.78; Cl 25.86; N 5.11.
syn-3-Chloro-2-hydroxy-3-(4-chlorophenyl)propionic
acid amide (syn-3e) was prepared according to
procedure b. Yield 2.13 g (91%), white solid, mp 172–
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5-(α-HALOBENZYL)- AND 5-BENZYLIDENE-2,2-DIMETHYL-1,3-OXAZOLIDIN-4-ONES
2807
173°C. IR spectrum, ν, cm–1: 3452, 3344 (NH2), 1671
7.0 Hz), 4.17 q (2H, CH2, J = 7.0 Hz), 4.66 d (1H,
1
[C(О)NH2]. H NMR spectrum, δ, ppm: 4.32 d (1H,
CH2, J = 8.7 Hz), 5.33 d (1H, CH3, J = 8.7 Hz), 7.57
d.d (1H, H5Ar, J = 7.6 Hz), 7.73 d (1H, H6Ar, J =
7.8 Hz), 7.74 d.d (1H, H4Ar, J = 7.8 Hz), 7.95 d (1H,
H3Ar, J = 7.6 Hz). Found, %: C 48.76; H 4.01; Hlg
31.43. C12H12ClF3O3. Calculated, %: C 48.58; H 4.08;
Cl 11.95; F 19.21.
CH2, J = 5.0 Hz), 5.32 d (1H, CH3, J = 5.0 Hz), 7.20
br.s (1H, NH), 7.29 br.s (1H, NH), 7.38 d (2H, H2,6
,
Ar
J = 8.6 Hz), 7.71 d (2H, H3,5Ar, J = 8.6 Hz). Found, %:
C 46.31; H 3.83; Cl 30.36; N 5.91. C9H9Cl2NO2.
Calculated, %: C 46.18; H 3.88; Cl 30.29; N 5.98.
trans-3-(4-Nitrophenyl)glycidic acid (trans-5a).
To a solution of 0.40 g (1.6 mmol) of syn-4a in MeOH
(15 mL) was added 0.66 g (4.8 mmol) of K2CО3. The
mixture was stirred at room temperature for 7 h, then
poured into water. The aqueous solution was extracted
with ethyl acetate (3×4 mL), the extract was dried over
Na2SO4, and the solvent was removed. Yield 0.21 g
(64%), yellow solid, mp 193–195°C. IR spectrum, ν,
3-Chloro-2-hydroxy-3-arylpropionic acids (4a, 4b).
A mixture of 2 mmol of the corresponding 5- (chloro-
benzyl)-2,2-dimethyl-1,3-oxazolidin-4-one 2 or 3-chloro-
2-hydroxy-3-arylpropionic acid amides 3 or 3-aryl-2,3-
epoxypropionic acid amides 1 and 3 mL of conc. HCl
was refluxed with stirring for 1–2 h. After completion
of the reaction the mixture was poured into water
(25 mL). In the case of compound 4a the formed
precipitate was filtered off, washed with water, and
dried in air. In the case of compound 4b the formed oil
was separated from water with a separatory funnel.
The aqueous layer was extracted with diethyl ether
(2×5 mL). The oil fraction and extract were combined,
dried over Na2SO4 and concentrated to give a pure
sample.
1
cm–1: 1714 (C=О), 1538 (NO2). H NMR spectrum, δ,
ppm: 3.70 br.s (1H, CH2), 4.34 br.s (1H, CH3), 7.64 d
(2H, H2,6Ar, J = 8.5 Hz), 8.23 d (2H, H3,5Ar, J = 8.5 Hz).
Found, %: C 51.33; H 3.42; N 6.58. C9H7NO5.
Calculated, %: C 51.68; H 3.37; N 6.70.
2-Hydroxy-3-arylacrylic acids (6a–6e). A mixture
of 2 mmol of 5-benzylidene-2,2-dimethyl-1,3-oxazol-
idin-4-one 7a–7e or 5-(halobenzyl)-2,2-dimethyl-1,3-
oxazolidin-4-one 2c–2e and 3 mL of conc. HCl was
refluxed for 15 min or 1 h with stirring, then poured
into water (25 mL) and extracted with ethyl acetate
(3×5 mL). The extracts were dried over Na2SO4, and
the solvent was removed.
syn-3-Chloro-2-hydroxy-3-(4-nitrophenyl)propionic
acid (syn-4a). Yield 0.30 g (62%), yellow solid, mp
169–170°C. IR spectrum, ν, cm–1: 3483 (ОH), 1726
(C=О), 1519 (NO2). 1H NMR spectrum, δ, ppm: 4.44 d
(1H, CH2, J = 6.9 Hz), 5.36 d (1H, CH3, J = 6.9 Hz),
7.76 d (2H, H2,6Ar, J = 8.8 Hz), 8.21 d (2H, H3,5Ar, J =
8.8). Found, %: C 43.89; H 3.21; Cl 14.57; N 5.62.
C9H8ClNO5. Calculated, %: C 44.01; H 3.28; Cl 14.43;
N 5.70.
2-Hydroxy-3-(4-nitrophenyl)acrylic acid (6a).
Yield 35 g (83%), yellow solid, mp 186–187°C (mp
188°C [33], 186°C [37], 192°C [38]). IR spectrum, ν,
1
cm–1: 3475 (ОH), 1681 (C=О), 1510 (NO2). H NMR
syn-3-Chloro-2-hydroxy-3-[2-(trifluoromethyl)-
phenyl]propionic acid (syn-4b). Yield 0.48 g (89%),
yellow oil. IR spectrum, ν, cm–1: 3416, 3084 (ОH),
spectrum, δ, ppm: 6.48 s (1H, =CH), 7.96 d (2H,
H2,6Ar, J = 8.9 Hz), 8.17 d (2H, H3,5Ar, J = 8.9 Hz).
Found, %: C 51.32; H 3.41; N 6.68. C9H7NO5.
Calculated, %: C 51.68; H 3.37; N 6.70.
1
1733 (C=О). H NMR spectrum, δ, ppm: 4.57 d (1H,
CH2, J = 8.7 Hz), 5.34 d (1H, CH3, J = 8.7 Hz), 7.56
d.d (1H, H5Ar, J = 7.6, J = 7.5 Hz), 7.58–7.78 m (2H,
2-Hydroxy-3-[4-(trifluoromethyl)phenyl]acrylic
acid (6b). Yield 0.41 g (87%), white solid, mp 200–
201°C (mp 170°C [38]). IR spectrum, ν, cm–1: 3467
(ОH), 1688 (C=О), 1510 (NO2). 1H NMR spectrum, δ,
ppm: 6.46 s (1H, =CH), 7.69 d (2H, H3,5Ar, J = 8.3 Hz),
7.95 d (2H, H2,6Ar, J = 8.2 Hz). Found, %: C 51.85; H
3.15; F 24.67. C10H7F3O3. Calculated, %: C 51.74; H
3.04; F 24.55.
H4 and H6Ar), 7.96 d (1H, H3Ar, J = 7.8 Hz). Found,
Ar
%: C 44.83; H 3.21; Hlg 34.70. C10H8ClF3O3. Calculated,
%: C 44.71; H 3.00; Cl 13.20; F 21.22.
Ethyl syn-3-chloro-2-hydroxy-3-[2-(trifluoromethyl)-
phenyl]propionate (syn-4b'). A mixture of 0.61 g
(2 mmol) of syn-5-α-chloro[2-(trifluoromethyl)benzyl]-
2,2-dimethyl-1,3-oxazolidin-4-one syn-2b, 3 mL of
conc. HCl and 3 mL of EtOH were refluxed with
stirring for 1 h, then washed with water. The organic
layer was separated and dried on air. Yield 0.49 g
(82%). IR spectrum, ν, cm–1: 3397 (ОH), 1726 (C=О).
1H NMR spectrum, δ, ppm: 1.19 t (3H, CH3, J =
2-Hydroxy-3-phenylacrylic acid (6c). Yield 0.26
(79%, from syn-2c), 0.24 (72%, from anti-2c'), 0.25
(76%, from syn-2c), 0.23 (71%, from cis-7c), 0.28 g
(85%, from trans-7c), pale yellow solid, mp 157–158°C
(mp 151–153°C [29], 159–161°C [39]). IR spectrum,
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MAMEDOV et al.
ν, cm–1: 3433, 3283 (ОH), 1732 (C=О). H NMR
spectrum, δ, ppm: 6.40 s (1H, =CH), 7.23 d.d (1H,
H4Ph, J = 7.4 Hz), 7.35 d.d (2H, H3,5Ph, J = 7.8, J =
7.4 Hz), 7.75 d (2H, H2,6 Ph, J = 7.7 Hz). Found, %: C
65.74; H 4.81. C9H8O3. Calculated, %: C 65.85; H 4.91.
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2-Hydroxy-3-(4-bromophenyl)acrylic acid (6d).
Yield 0.34 (71%, from syn-2d), 0.36 g (75%, from
trans-7d), gray solid, mp 165–166°C. IR spectrum, ν,
cm–1: 3469, 3341 (ОH), 1688 (C=О). 1H NMR
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H3,5Ar, J = 8.5 Hz), 7.71 d (2H, H2,6Ar, J = 8.5 Hz).
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Calculated, %: C 44.47; H 2.90; Br 32.87.
2-Hydroxy-3-(4-chlorophenyl)acrylic acid (6e).
Yield 0.31 (79%, from syn-2d), 0.36 g (83%, from
trans-7e), gray solid, mp 190–191°C (mp 188°C [36],
183°C [38], 182°C [40]). IR spectrum, ν, cm–1: 3465
1
(ОH), 1688 (C=О). H NMR spectrum, δ, ppm: 6.32 s
(1H, =CH), 7.32 d (2H, H3,5Ar, J = 8.6 Hz), 7.69 d (2H,
H2,6Ar, J = 8.6 Hz). Found, %: C 54.03; H 3.59; Cl
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17.85.
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5-Benzylidene-2,2-dimethyl-1,3-oxazolidin-4-ones
7 were prepared according to the procedure described
in [21] from 5 mmol of the corresponding 5-(halo-
benzyl)-2,2-dimethyl-1,3-oxazolidin-4-ones 2.
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oxazolidin-4-one (trans-7a). Yield 0.88 g (71%),
yellow solid, mp 227–228°C. IR spectrum, ν, cm–1:
3184, 3063 (NH2), 1706 (C=О), 1592, 1510 (NO2). 1H
NMR spectrum, δ, ppm: 1.57 s (6H, 2 Ме), 6.16 s (1H,
=CH), 7.86 d (2H, H2,6Ar, J = 8.8 Hz), 8.19 d (2H,
H3,5Ar, J = 8.8 Hz), 9.95 br.s (1H, NH). Found, %: C
58.63; H 4.82; N 11.09. C12H12N2O4. Calculated, %: C
58.06; H 4.87; N 11.29.
trans-5-(4-Chlorobenzylidene)-2,2-dimethyl-1,3-
oxazolidin-4-one (trans-7e). Yield 0.87 g (73%),
yellow solid, mp 118–120°C. IR spectrum, ν, cm–1:
1
3189 (NH2), 1707 (C=О). H NMR spectrum, δ, ppm:
1.46 s (6H, 2 Ме), 6.18 s (1H, =CH), 7.29 d (2H,
H3,5Ar, J = 8.6 Hz), 7.82 d (2H, H2,6Ar, J = 8.6 Hz), 7.23
br.s (1H, NH), 9.68 br.s (1H, NH). Found, %: C 60.32;
H 5.15; Cl 14.22; N 5.77. C12H12ClNO2. Calculated,
%: C 60.64; H 5.09; Cl 14.92; N 5.89.
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This work was financially supported by the Russian
Science Foundation (grant no 14-23-00073-p).
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5-(α-HALOBENZYL)- AND 5-BENZYLIDENE-2,2-DIMETHYL-1,3-OXAZOLIDIN-4-ONES
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