A highly efficient methodology for 5-methyl-3-aryl-2-thiooxazolidin-4-ones using lithium perchlorate in DIPEA mediated synthesis

Article abstract of DOI:10.1002/jhet.369

(Chemical Equation Presented) An efficient methodology for the synthesis of 5-methyl-3-aryl-2-thiooxazolidin-4-ones from aryl isothiocyanates has been developed. Aryl isothiocyanates, synthesized from various anilines, were converted to the desired compounds by treating with ethyl lactate in presence of DIPEA and catalytic amount of lithium perchlorate. This method provides a convenient and cost-effective strategy, with no specific purification protocol.

Full text of DOI:10.1002/jhet.369

734
A Highly Efficient Methodology for 5-Methyl-3-aryl-2-
thiooxazolidin-4-ones Using Lithium Perchlorate in DIPEA
Mediated Synthesis
Vol 47
Gopal L. Khatik, Anang Pal, Tushar D. Apsunde, and Vipin A. Nair*
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research
(NIPER), Mohali, Punjab 160 062, India
*E-mail: vnair@niper.ac.in
Received September 21, 2009
DOI 10.1002/jhet.369
Published online 3 May 2010 in Wiley InterScience (www.interscience.wiley.com).
An efficient methodology for the synthesis of 5-methyl-3-aryl-2-thiooxazolidin-4-ones from aryl iso-
thiocyanates has been developed. Aryl isothiocyanates, synthesized from various anilines, were con-
verted to the desired compounds by treating with ethyl lactate in presence of DIPEA and catalytic
amount of lithium perchlorate. This method provides a convenient and cost-effective strategy, with no
specific purification protocol.
J. Heterocyclic Chem., 47, 734 (2010).
INTRODUCTION
anilines 1(a–j). A model reaction of 4-chlorophenyl iso-
thiocyanate with ethyl lactate was experimented under
various reaction conditions like sodium hydride, potas-
sium-tert-butoxide, sodium metal, potassium hydroxide,
1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), and N,N-dii-
sopropylethylamine (DIPEA) (Experiments 1–6; Table
1), but the yields obtained were quite disappointing.
This prompted us to employ an alternate strategy based
on the assumption that the condensation between the
reactants would become more facile if their reactivity
could be enhanced by adequate co-ordination. Quite
interestingly, as in agreement with our notion, a stirring
solution of 4-chlorophenyl isothiocyanate and ethyl lac-
tate in dichloroethane (DCE) when refluxed in presence
of DIPEA and lithium perchlorate (Scheme 2) showed a
drastic improvement in the yields (Experiments 8–10;
Table 1); though the product was not formed when ei-
ther of these was solely employed (Experiments 6 and
7; Table 1).
Oxazolidinones and thiooxazolidinones form an inte-
gral part of many drugs/intermediates [1,2]. They are
well known as chiral directing agents in asymmetric
synthesis [3,4]. Thiooxazolidinones were reported for
various activities such as potassium channel openers [5],
antidiabetics [2], and anticonvulsants [6]. A perusal of
the literature shows that there is no report on the synthe-
sis of 3-aryl-2-thiooxazolidin-4-ones having an a-proton,
and the available methods in the case of 5,5-dimethyl-3-
aryl-2-thiooxazolidin-4-ones, which lack a-protons are
poor yielding (Scheme 1) [7–10]. Above all, the
reported strategies relied on the kind of isothiocyanates
used, and an extrapolation of the methodology to some
of the substrates discussed in this article failed primarily
due to the harsh reaction conditions [7,8] and the strong
base employed [9], leading to the formation of very lit-
tle of the desired product [10] together with unwanted
side-products. The tight legislation on the maintenance
of greenness in synthetic pathways and processes
demands to prevent waste and minimize energy require-
ments which unfortunately could not be met in uneco-
nomical low yielding reactions [11].
From the results obtained a plausible reaction mecha-
nism could be depicted as shown in Figure 1. Lithium
co-ordinates with the hydroxyl group of ethyl lactate
forming the OALi bond and simultaneously generates
perchloric acid which reacts with DIPEA to produce the
protonated base and perchlorate anion. Further, the alk-
oxide attacks the thiocarbonyl carbon of the aryl isothio-
cyanate resulting in an intramolecular cyclization
followed by the protonation of the ethoxy group
thereby expelling it as a good leaving group to afford
RESULTS AND DISCUSSION
Various aryl isothiocyanates 2(a–j) were prepared by
previously reported method [12] from corresponding
C
V
2010 HeteroCorporation

May 2010
A Highly Efficient Methodology for 5-Methyl-3-aryl-2-thiooxazolidin-4-ones
Using Lithium Perchlorate in DIPEA Mediated Synthesis
735
Scheme 1. Reported strategy for the synthesis of 5,5-dimethyl-3-aryl-2-thiooxazolidin-4-ones lacking a-proton.
5-methyl-3-aryl-2-thiooxazolidin-4-ones with the regen-
eration of lithium perchlorate in the final step.
[16], Baylis-Hillman reaction [17], aromatic and heter-
oatom acylation [18], and Nazarov cyclization [19].
Further studies were carried out to determine the stoi-
chiometric quantity of the functional group activator.
Based on percentage conversion calculated from GC-MS
traces at various concentrations of 0.1, 0.2, 0.6, and 1.2
equivalent of LiClO4 (Fig. 2); it was ascertained that 0.2
equivalent of the Lewis acid would suffice the purpose.
We also observed that solvents have a profound influ-
ence over the course of the reaction (Table 2). The reac-
tion failed in polar protic medium. Aprotic solvents like
toluene and benzene afforded the product in good yields
while 1,2-dichloroethane turned out to be the best.
To generalize the methodology the standardized con-
dition was employed on various substituted aryl isothio-
cyanates, and the respective products were obtained in
good yields though the nature of the substituents was
found to affect the course of the reaction.
Since lithium shows diagonal relationship with mag-
nesium; magnesium perchlorate was also tested, but the
reaction afforded poor results and so was the case with
zinc perchlorate (Experiments 12 and 13; Table 1). Sur-
prisingly, comparative results could not be obtained
when lithium perchlorate was used with triethylamine
(TEA) instead of DIPEA (Experiment 11; Table 1). The
reason could be attributed to DIPEA having more basic
character over TEA. Also the higher boiling point of
DIPEA is advantageous under the reflux conditions. The
Lewis acid catalyst lithium perchlorate was chosen
based on the well known fact that lithium possess better
co-ordination power due to its least ionic radius
˚
(0.76 A) than other alkali metals and therefore the
higher charge:size ratio increases its covalent character.
Also lithium perchlorate is cheap, commercially avail-
able and soluble in various organic solvents. The effi-
ciency of lithium perchlorate is well established in vari-
ous reactions like Diels-Alder reaction [13,14], Friedel-
Crafts acylation [15], aminophosphonation of aldehydes
Electron withdrawing functional groups which gener-
ally increase the electrophilicity of aryl isothiocyanate
provided better yields (Entries 1–7; Table 3), where as
electron donating groups led to longer reaction time
Table 1
Effect of reagent/catalyst in the synthesis of 5-methyl-3-aryl-2-thiooxazolidin-4-one.a
Reaction condition
Experiment
Reagentc
Catalystd
Solvent
% conv. (GC-MS)
Isolated yield (%)b
1
2
3
NaH
KOtBu
Nad
–
DMF
DMF
Toluene
DMF
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
15
15
24
15
20
0
10
12
23
10
10
0
–
–
4
KOH
DBU
DIPEA
–
DIPEA
DIPEA
DIPEA
TEA
–
5
6
–
–
7
8
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
0
0
c
89
88
92
71
25
40
88
87
90
70
20
30
e
9
10
11
12
13
DIPEA
DIPEA
Mg(ClO4)2
Zn(ClO4)2. 6H2O
a The reaction was carried out by stirring a mixture of 4-chlorophenyl isothiocyanate (1.18 mmol, 1.0 equiv) and ethyl lactate (1.42 mmol, 1.2
equiv) in presence of reagent and/or catalyst and solvent (10 mL) at room temperature for 10 min and then refluxing for 1 h.
b The product was characterized by NMR and mass spectroscopic methods.
c 1.2 equiv was used.
d 0.2 equiv was used.
e 0.6 equiv was used.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

736
G. L. Khatik, A. Pal, T. D. Apsunde, and V. A. Nair
Vol 47
Scheme 2. Synthesis of 5-methyl-3-aryl-2-thiooxazolidin-4-ones.
Nicolet Impact 400 spectrometer as KBr pellets for solid sam-
ples. Mass spectra were recorded on POLARIS Q (Thermo
Scientific) GC-MSMS spectrometer and elemental analyses
were done by Varion-EL elemental analyzer. The reactions
were monitored by TLC (Merck). Evaporation of solvents was
performed under reduced pressure using a Buchi rotary evapo-
rator. Melting points are uncorrected.
with lesser yields (Entries 8–10; Table 3). The reaction
conditions were also compatible with disubstituted aryl
isothiocyanates (Entries 6–7 and 9–10; Table 3).
In conclusion, an efficient and viable synthetic strat-
egy for synthesis of 5-methyl-3-aryl-2-thiooxazolidin-4-
ones has been developed.
Commercial grade reagents and solvents were used without
further purification; ethyl lactate, lithium perchlorate, zinc per-
chlorate hexahydrate, magnesium perchlorate, 4-fluoro-3-chlor-
oaniline, 4-chloro-3-trifluoromethylaniline (Aldrich), N,N-diiso-
propylethylamine, triethylamine, 4-bromoaniline, 4-fluoroani-
line, 4-aminobenzonitrile, 4-methylaniline, 3,4-dimethylaniline,
3,4-dimethoxyaniline, thiophosgene, sodium metal, sodium
hydride (60% suspension in mineral oil), potassium tert-butox-
ide, DBU, 1,4-dioxane, (Spectrochem); 4-chloroaniline
(Merck); sodium hydrogen carbonate, THF, toluene (CDH);
DCE (Loba Chemie), DME (Sigma), benzene, DMF (SISCO),
3-nitroaniline (S.D. Fine chemicals), potassium hydroxide
(Qualigens).
EXPERIMENTAL
The 1H and 13C NMR spectra were recorded at 400 MHz
and 100 MHz, respectively on a Bruker Avance DPX 400 (400
MHz) spectrometer in CDCl3 using TMS as an internal stand-
1
ard. The chemical shifts (d) for H and 13C are given in ppm
relative to residual signals of the solvent (CHCl3). Coupling
constants are given in Hz. The following abbreviations are
used to indicate the multiplicity: s, singlet; d, doublet; m, mul-
tiplet; bs, broad signal. The IR spectra were recorded on a
General procedure for the synthesis of aryl
isothiocyanates. In a 100 mL RB flask, a solution of sodium
hydrogen carbonate (5.5 g, 65.7 mmol) in 20 mL water was
stirred for 10 min and to it dichloromethane (20 mL) was
added followed by 4-chloroaniline (2.0 mL, 21.9 mmol). The
reaction mixture was cooled to 0ꢀC, thiophosgene (2.5 mL,
32.85 mmol) was introduced dropwise over a period of 30 min
and continuously stirred at room temperature for 1 h. The
workup of the reaction mixture was carried out in dichlorome-
thane and dried over anhydrous sodium sulphate. The organic
layer upon concentration afforded a crude gummy compound,
Figure 1.
5-methyl-3-aryl-2-thiooxazolidin-4-ones.
A
plausible reaction mechanism for the formation of
Figure 2. GC-MS study of model reaction at various concentrations of
LiClO4.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2010
A Highly Efficient Methodology for 5-Methyl-3-aryl-2-thiooxazolidin-4-ones
Using Lithium Perchlorate in DIPEA Mediated Synthesis
737
Table 2
Effect of solvent in the synthesis of 5-methyl-3-aryl-2-thiooxazolidin-4-one.a
Experiment
Reagentb
Catalystc
Solvent
% conv. (GC-MS)
Isolated yield (%)d
1
2
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
Neat (80ꢀC)
Toluene
Benzene
DME
10
85
86
70
92
85
36
0
10
81
83
66
90
81
33
0
3
4
5
DCE
6
7
Dioxane
THF
DMF
DMSO
Ethanol
Methanol
8
9
0
0
10
11
0
0
0
0
a The reaction was carried out by stirring a mixture of 4-chlorophenyl isothiocyanate (1.18 mmol, 1.0 equiv) and ethyl lactate (1.42 mmol, 1.2
equiv) in presence of reagent and/or catalyst and solvent (10 mL) at room temperature for 10 min and then refluxing for 1 h.
b 1.2 equiv was used.
c 0.2 equiv was used.
d The product was characterized by NMR and mass spectroscopic methods.
which was recrystallized in hexane under cold condition. The
precipitate was filtered and dried to get the desired compound
(Yield: 3.0 g, 81%, white solid). The formation of the product
was confirmed by analytical and spectral methods.
4-Chlorophenyl isothiocyanate (2a). Yield: 81%, white
solid; NMR (1H, 400 MHz, CDCl3) d 7.16 (d, J ¼ 8.8 Hz,
2H), 7.33 (d, J ¼ 8.8 Hz, 2H); MS (m/z): 169.03 (Mþ).
4-Bromophenyl isothiocyanate (2b). Yield: 82%, white
solid; NMR (1H, 400 MHz, CDCl3) d 7.10 (d, J ¼ 8.8 Hz, 2H),
7.48 (d, J ¼ 8.8 Hz, 2H); MS (m/z): 213.03 (Mþ), 215.03 (Mþ2).
4-Fluorophenyl isothiocyanate (2c). Yield: 81%, colourless
oil; NMR (1H, 400 MHz, CDCl3) d 7.00–7.09 (m, 2H), 7.19–
7.24 (m, 2H); MS (m/z): 153.14 (Mþ).
3-Nitrophenyl isothiocyanate (2e). Yield: 75%, yellow
solid; NMR (1H, 400 MHz, CDCl3) d 7.56 (d, J ¼ 8.8 Hz,
2H), 8.06 (s, 1H), 8.10–8.15 (m, 1H); MS (m/z): 180.09 (Mþ).
3-Chloro-4-fluorophenyl isothiocyanate (2f). Yield: 75%,
colourless oil; NMR (1H, 400 MHz, CDCl3) d 7.09–7.16 (m,
2H), 7.29–7.37 (m, 1H); MS (m/z): 187.01 (Mþ).
4-Chloro-3-trifluoromethylphenyl isothiocyanate (2g). Yield:
70%, colourless oil; NMR (1H, 400 MHz, CDCl3) d 7.31–
7.34 (m, 1H), 7.42–7.54 (m, 2H); MS (m/z): 237.07 (Mþ).
4-Methylphenyl isothiocyanate (2h). Yield: 90%, brownish
solid; NMR (1H, 400 MHz, CDCl3) d 2.36 (s, 3H), 7.11–7.16
(m, 4H); MS (m/z): 149.08 (Mþ).
3,4-Dimethylphenyl isothiocyanate (2i). Yield: 92%, brown
oil; NMR (1H, 400 MHz, CDCl3) d 2.26 (s, 6H), 6.97 (d, J ¼
8.0 Hz, 1H), 7.02 (s, 1H), 7.09 (d, J ¼ 8.0 Hz, 1H); MS (m/z):
163.09 (Mþ).
4-Cyanophenyl isothiocyanate (2d). Yield: 79%, white
solid; NMR (1H, 400 MHz, CDCl3) d 7.31 (d, J ¼ 8.8 Hz,
2H), 7.66 (d, J ¼ 8.8 Hz, 2H); MS (m/z): 160.07 (Mþ).
Table 3
Synthesis of 5-methyl-3-aryl-2-thiooxazolidin-4-ones.a
Entry
Aryl isothiocyanate
R1
R2
Reaction time (h)
Product
% conv. (GC-MS)
Isolated yield (%)b
1
2
2a
2b
2c
2d
2e
2f
2g
2h
2i
Cl
Br
H
H
1.0
1.5
1.0
1.5
1.5
2.0
2.0
1.0
1.5
1.5
3a
3b
3c
3d
3e
3f
3g
3h
3i
92
77
87
82
79
70
74
70
78
71
90
75
85
80
75
69
72
65
70
70
3
4
F
CN
H
H
H
5
NO2
Cl
CF3
H
Me
MeO
6
7
F
Cl
8
9
10
Me
Me
MeO
2j
3j
a The reaction was carried out by stirring a mixture of aryl isothiocyanate (1.18 mmol, 1.0 equiv) and ethyl lactate (1.42 mmol, 1.2 equiv) in pres-
ence of DIPEA (1.42 mmol, 1.2 equiv) and LiClO4 (0.24 mmol, 0.2 equiv) in DCE (10 mL) at room temperature for 10 min and then refluxing for
1–2 h.
b The product was characterized by NMR and mass spectroscopic methods.
Journal of Heterocyclic Chemistry
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G. L. Khatik, A. Pal, T. D. Apsunde, and V. A. Nair
Vol 47
7.2 Hz, 3H), 5.12–5.17 (m, 1H), 7.24–7.33 (m, 2H), 7.43–7.46
(m, 1H); NMR (13C, 100 MHz, CDCl3) d 16.62, 78.78,
117.27, 117.50, 127.71, 127.79, 130.18, 157.28, 159.80,
172.74, 188.51; MS (m/z): 259.05 (Mþ); C10H7ClFN2O2S
Calcd: C, 46.25; H, 2.72; N, 5.39; S, 12.35; Found: C, 46.27;
H, 2.75; N, 5.43; S, 12.39.
5-Methyl-3-(4-chloro-3-trifluoromethylphenyl)-2-thiooxazo-
lidin-4-one (3g). Yield: 72%, white solid; mp 178–181ꢀC;
FTIR (KBr) m: 1781 cmꢁ1; NMR (1H, 400 MHz, CDCl3) d
1.80 (d, J ¼ 7.2 Hz, 3H), 5.15–5.20 (m, 1H), 7.52 (d, J ¼ 8.8
Hz, 1H), 7.69 (d, J ¼ 8.8 Hz, 1H), 7.72 (s, 1H); NMR (13C,
100 MHz, CDCl3) d 16.65, 78.87, 123.42, 127.00, 127.06,
129.92, 130.81, 131.93, 132.61, 172.53, 187.98; MS (m/z):
309.01 (Mþ); C11H7ClF3NO2S Calcd: C, 42.66; H, 2.28; N,
4.52; S, 10.35; Found: C, 42.70; H, 2.31; N, 4.55; S, 10.34.
5-Methyl-3-(4-methylphenyl)-2-thiooxazolidin-4-one
(3h). Yield: 65%, white solid; mp 109–111ꢀC; FTIR (KBr) m:
1769 cmꢁ1; NMR (1H, 400 MHz, CDCl3) d 1.76 (d, J ¼ 7.2
Hz, 3H), 2.43 (s, 3H), 5.11–5.16 (m, 1H), 7.21 (d, J ¼ 8.0 Hz,
2H), 7.34 (d, J ¼ 8.0 Hz, 2H); NMR (13C, 100 MHz, CDCl3)
d 16.69, 21.34, 78.67, 127.23, 129.60, 130.22, 140.09, 173.35,
189.63; MS (m/z): 222.09 (Mþ1); C11H11NO2S Calcd: C,
59.71; H, 5.01; N, 6.33; S, 14.49; Found: C, 59.68; H, 5.04;
N, 6.28; S, 14.51.
3,4-Dimethoxyphenyl isothiocyanate (2j). Yield: 88%,
white solid; NMR (1H, 400 MHz, CDCl3) d 3.37 (s, 6H), 6.65
(s, 1H), 6.69–6.75 (m, 2H); MS (m/z): 195.14 (Mþ).
General procedure for the synthesis of 5-methyl-3-aryl-2-
thiooxazolidin-4-one. To a solution of 4-chlorophenyl isothio-
cyanate (0.2 g, 1.18 mmol, 1.0 equiv) in 1,2-dichloroethane
(10 mL), ethyl lactate (0.17 mL, 1.42 mmol, 1.2 equiv), N,N-
diisopropylethylamine (0.24 mL, 1.42 mmol, 1.2 equiv), and
lithium perchlorate (0.026 g, 0.24 mmol, 0.2 equiv) were
added. It was refluxed for 1 h, and the reaction mixture was
cooled, washed with water, and concentrated. The crude prod-
uct was dissolved in minimum amount of dichloromethane,
precipitated with excess of hexane, filtered, and dried (Yield:
0.26 g, 90%, white solid). The compound was identified by
spectral and analytical methods.
5-Methyl-3-(4-chlorophenyl)-2-thiooxazolidin-4-one (3a). Yield:
90%, white solid; mp 111–114ꢀC; FTIR (KBr) m: 1763 cmꢁ1
;
NMR (1H, 400 MHz, CDCl3) d 1.77 (d, J ¼ 6.8 Hz, 3H),
5.11–5.17 (m, 1H), 7.30 (d, J ¼ 8.8 Hz, 2H), 7.51 (d, J ¼ 8.8
Hz, 2H); NMR (13C, 100 MHz, CDCl3) d 16.66, 78.71,
128.86, 129.78, 130.64, 135.84, 172.91, 188.79; MS (m/z):
241.00 (Mþ); C10H8ClNO2S Calcd: C, 49.69; H, 3.34; N,
5.80; S, 13.27; Found: C, 49.72; H, 3.38; N, 5.85; S, 13.33.
5-Methyl-3-(4-bromophenyl)-2-thiooxazolidin-4-one
(3b). Yield: 75%, white solid; mp 144–147ꢀC; FTIR (KBr) m:
1771 cmꢁ1; NMR (1H, 400 MHz, CDCl3) d 1.78 (d, J ¼ 7.2
Hz, 3H), 5.12–5.17 (m, 1H), 7.24 (d, J ¼ 8.8 Hz, 2H), 7.67 (d,
J ¼ 8.8 Hz. 2H); NMR (13C, 100 MHz, CDCl3) d 16.67, 78.74,
123.96, 129.12, 131.16, 132.77, 172.86, 188.71; MS (m/z):
285.01(Mþ), 287.01(Mþ2); C10H8BrNO2S Calcd: C, 41.97; H,
2.82; N, 4.89; S, 11.21; Found: C, 41.95; H, 2.80; N, 4.94; S,
11.23.
5-Methyl-3-(3,4-dimethylphenyl)-2-thiooxazolidin-4-
one (3i). Yield: 70%, white solid; mp 113–115ꢀC; FTIR
(KBr) m: 1769 cmꢁ1; NMR (1H, 400 MHz, CDCl3) d 1.73 (d,
J ¼ 7.2 Hz, 3H), 2.30 (s, 6H), 5.07–5.12 (m, 1H), 7.02 (s,
1H), 7.04 (d, J ¼ 7.6 Hz, 1H), 7.25 (d, J ¼ 7.6 Hz, 1H);
NMR (13C, 100 MHz, CDCl3) d 16.69, 19.69, 19.89, 78.70,
124.76, 128.24, 129.79, 130.69, 138.28, 138.85, 173.46,
189.81; MS (m/z): 235.09 (Mþ); C12H13NO2S Calcd: C, 61.25;
H, 5.57; N, 5.95; S, 13.63; Found: C, 61.21; H, 5.61; N, 5.99;
S, 13.65.
5-Methyl-3-(3,4-dimethoxyphenyl)-2-thiooxazolidin-4-
one (3j). Yield: 70%, white solid, mp 145–147ꢀC; FTIR (KBr)
m: 1768 cmꢁ1; NMR (1H, 400 MHz, CDCl3) d 1.76 (d, J ¼
6.8 Hz, 3H), 3.89 (s, 3H), 3.92 (s, 3H), 5.09–5.14 (m, 1H),
6.80 (s, 1H), 6.87 (d, J ¼ 8.8 Hz, 1H), 6.97 (d, J ¼ 8.8 Hz,
1H); NMR (13C, 100 MHz, CDCl3) d 16.64, 56.05, 56.13,
78.62, 110.73, 111.20, 120.04, 124.80, 149.55, 150.02, 173.39,
189.76; MS (m/z): 267.08 (Mþ); C12H13NO4S Calcd: C, 53.92;
H, 4.90; N, 5.24; S, 12.00; Found: C, 53.94; H, 4.89; N, 5.30;
S, 11.95.
5-Methyl-3-(4-fluorophenyl)-2-thiooxazolidin-4-one
(3c). Yield: 85%, white solid; mp 93–96ꢀC; FTIR (KBr) m:
1771 cmꢁ1; NMR (1H, 400 MHz, CDCl3) d 1.76 (d, J ¼ 6.8
Hz, 3H), 5.11–5.16 (m, 1H), 7.19–7.25 (m, 2H), 7.30–7.35 (m,
2H); NMR (13C, 100 MHz, CDCl3) d 16.63, 78.69, 116.51,
116.74, 129.49, 129.58, 161.66, 164.15, 173.08, 189.16; MS
m/z: 225.10 (Mþ); C10H8FNO2S Calcd: C, 53.32; H, 3.58; N,
6.22; S, 14.24; Found: C, 53.35; H, 3.55; N, 6.27; S, 14.26.
5-Methyl-3-(4-cyanophenyl)-2-thiooxazolidin-4-one
(3d). Yield: 80%, white solid; mp 202–205ꢀC; FTIR (KBr) m:
1774, 2231 cmꢁ1; NMR (1H, 400 MHz, CDCl3) d 1.73 (d, J
¼ 6.8 Hz, 3H), 5.14–5.20 (m, 1H), 7.53 (d, J ¼ 8.8 Hz, 2H),
7.83 (d, J ¼ 8.8 Hz, 2H); NMR (13C, 100 MHz, CDCl3) d
16.65, 78.83, 113.69, 117.64, 128.49, 133.32, 135.98, 172.46,
187.77; MS (m/z): 232.10 (Mþ); C11H8N2O2S Calcd: C, 56.88;
H, 3.47; N, 12.06; S, 13.81; Found: C, 56.92; H, 3.51; N,
12.10; S, 13.86.
Acknowledgment. The authors thank the Department of Science
and Technology, Government of India for the research funding.
REFERENCES AND NOTES
5-Methyl-3-(3-nitrophenyl)-2-thiooxazolidin-4-one (3e). Yield:
75%, light yellow solid; mp 151–154ꢀC; FTIR (KBr) m: 1769
cmꢁ1; NMR (1H, 400 MHz, CDCl3) d 1.80 (d, J ¼ 7.2 Hz,
3H), 5.19–5.24 (m, 1H), 7.75 (d, J ¼ 8.0 Hz, 2H), 8.30 (s,
1H), 8.34–8.37 (m, 1H); NMR (13C, 100 MHz, CDCl3) d
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3.16; N, 11.09; S, 12.68.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2010
A Highly Efficient Methodology for 5-Methyl-3-aryl-2-thiooxazolidin-4-ones
Using Lithium Perchlorate in DIPEA Mediated Synthesis
739
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