Synthesis of a new class of arylsulfonylethylsulfonylmethyloxazolines and thiazolines

Article abstract of DOI:10.1002/jhet.865

A new class of arylsulfonylethylsulfonylmethyl oxazolines and thiazolines were prepared using multistep, one-pot methodologies exploiting lanthanide alkoxides and under microwave irradiation. The microwave method provides an excellent approach in a single step with high yields.

Full text of DOI:10.1002/jhet.865

646
Synthesis of a New Class of
Vol 49
Arylsulfonylethylsulfonylmethyloxazolines and Thiazolines
Venkatapuram Padmavathi,* Bhumireddy Chinnachennaiahgari Venkatesh,
Chokkappagari Premakumari, and Adivireddy Padmaja
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India
*
E-mail: vkpuram2001@yahoo.com
Received October 17, 2010
DOI 10.1002/jhet.865
View this article online at wileyonlinelibrary.com.
A new class of arylsulfonylethylsulfonylmethyl oxazolines and thiazolines were prepared using multistep,
one-pot methodologies exploiting lanthanide alkoxides and under microwave irradiation. The microwave
method provides an excellent approach in a single step with high yields.
J. Heterocyclic Chem., 49, 646 (2012).
INTRODUCTION
RESULTS AND DISCUSSION
Oxazolines and thiazolines are important constituents of
numerous bioactive natural products of peptide origin.
Their wide range of antitumor, antiviral, and antibiotic
activities has fueled numerous synthetic investigations [1].
In addition, 2-oxazolines are excellent catalyst ligands
[2–4], protecting groups [5], and monomers for the cationic
ring-opening polymerization [6–10]. Thiazoles are important
building blocks for preparing various pharmaceuticals.
Recently, many natural products containing thiazole moiety
were isolated and most of them exhibit considerable cyto-
toxicities and antitumor potentials [11]. Though a number
of 2-substituted oxazolines and thiazolines are commer-
cially available, the modular synthesis of oxazolines and
thiazolines containing a wide range of functional side
chains would be advantageous for both biomedical and
materials science applications. A variety of methods have
been reported for the synthesis of oxazolines viz., cyclode-
hydration of amidoalcohols [12], cyclocondensation of
carboxylic acids [13], orthoesters [14], imidatehydrochlorides
[15], imino ether hydrochlorides [16], and nitriles [17] with
aminoalcohols[18]. Similarly, thiazolines are prepared
by the coupling of imidates and esters with aminothiols
[19], cyclodehydration of hydroxy thioamides [20], and
heterocyclic interconversions from oxazolines [21] or
oxazolidines [22]. Earlier, we have reported the synthesis of
2-oxazolines and 2-thiazolines from arylsulfonylacetic acid
methyl ester, arylmethanesulfonylacetic acid methyl ester
[23], and phenacylsulfonylacetic acid methyl ester [24].
In continuation of our interest, we, herein, report the
synthesis of a new class of oxazolines and thiazolines
from 2-(2-(arylsulfonyl) ethylsulfonyl)acetic acid (6).
The present communication deals with the synthesis of
oxazolines and thiazolines by traditional four-step three
intermediate route, one-pot methodology exploiting lantha-
nide alkoxides and microwave irradiation. The reactive
intermediate 2-(2-(arylsulfonyl)ethyl-sulfonyl)acetic acid (6)
was prepared as follows. The reaction of thiophenol (1)
with 2-chloroethanol followed by chlorination and oxida-
tion provided arylsulfonyl ethyl chloride (4). The reaction
of 4 with 2-mercaptoacetic acid gave 2-(2-(arylsulfonyl)
ethylthio)acetic acid (5), which on oxidation resulted in
6. Esterification of 6 produced methyl 2-(2-(arylsulfonyl)
ethyl-sulfonyl)acetate (7; Scheme 1).
The ester functionality in 7 was used to develop
oxazoline and thiazoline rings by multistep methodology.
The reaction of 7 with 2-aminoethanol provided N-(2-
hydroxyethyl)-2-(arylsulfonylethylsulfonyl)acetamide
(8). Chlorination of 8 with thionyl chloride furnished
N-(2-chloroethyl)-2-(arylsulfonylethylsulfonyl)acetamide
(9). Cyclocondensation of 9 with NaH afforded 2-((2-
(arylsulfonyl)ethylsulfonyl)methyl)-4,5-dihydrooxazole (10;
Scheme 2). In a similar way, the reaction of 7 with 2-
aminoethanethiol gave S-2-aminoethyl 2-(2-(arylsulfonyl)-
ethylsulfonyl)ethanethioate (11), which in the presence of
NaH in THF produced 2-((2-(arylsulfonyl) ethylsulfonyl)
methyl)-4,5-dihydrothiazole (12; Scheme 2, Method A).
Samarium chemistry was also exploited to prepare the
compounds 10 and 12 in one-pot methodology. Thus, the
reaction of 7 with 2-aminoethanol in the presence of
n-butyllithium complexed with 5–10% molar equivalent
of anhydrous samarium (III) chloride suspension in toluene
gave 10. Likewise, the compound 12 was obtained by
© 2012 HeteroCorporation

May 2012
Synthesis of a New Class of Arylsulfonylethylsulfonylmethyloxazolines and Thiazolines
647
Scheme 1
Scheme 3
Scheme 4
column chromatography. The structures of all the com-
1
pounds 6–12 are ascertained by H and 13C NMR spectra.
(See Tables 1–3.)
the reaction of 7 with aminoethanethiol in the presence
of samarium chloride and n-butyllithium (Scheme 3;
Method B).
CONCLUSIONS
The microwave assisted synthesis of compounds 10 and
12 was also carried out to establish the general validity
of this technique for the development of oxazolines and
thiazolines. The direct irradiation of compound 6 and
2-aminoethanol at 540 watts for 3–5 min gave the com-
pound 10. Similarly, the microwave irradiation of com-
pound 6 with 2-aminoethanethiol at 560 watts for 4–5 min
resulted in 12 (Scheme 4; Method C). The products 10
and 12 were isolated by solvent extraction and purified by
A new class of arylsulfonylethylsulfonylmethyl oxazo-
lines and thiazolines were synthesized from the synthetically
vulnerable intermediate 2-(2-(arylsulfonyl) ethylsulfonyl)-
acetic acid by traditional four-step three intermediate routes,
one-pot methodologies using samarium (III) chloride and
under microwave irradiation. The microwave methodology
provides an excellent approach in a single step with high
yields.
EXPERIMENTAL
Scheme 2
Melting points were determined in open capillaries on a Mel–
Temp apparatus and are uncorrected. The purity of the compounds
was checked by TLC (silica gel H, BDH, hexane/ethyl acetate, 3:1).
The IR spectra were recorded on a Thermo Nicolet IR 200 FTIR
spectrometer as KBr pellets, and the wave numbers were given
1
in cmꢀ1. The H NMR spectra were recorded in CDCl3/DMSO-d6
on a Jeol JNM l-400 MHz. The 13C NMR spectra were recorded
in CDCl3/DMSO-d6 on a Jeol JNM spectrometer operating at
l-100 MHz. All chemical shifts are reported in ppm using
TMS as an internal standard. The microanalyses were performed on
a Perkin–Elmer 240C elemental analyzer.
Multistep synthesis of 2-oxazolines and 2-thiazolines.
Methyl 2-(2-(arylsulfonyl)ethylsulfonyl)acetate (7). General
procedure. A solution of 2-(2-(arylsulfonyl)ethylsulfonyl)
acetic acid (6; 10 mmol) in methanol (10 mL) and Conc. H2SO4
(1 mL) was refluxed on a steam bath for 4–5 h. The contents of
the flask were cooled and poured onto crushed ice. The
solid separated was collected by filtration, washed with cold
water, and dried. The crude product was recrystallized
from methanol to get pure methyl 2-(2-(phenylsulfonyl)
ethylsulfonyl)acetate (7a; 68%), mp 121–123 ꢁC; methyl
2-(2-tosylethylsulfonyl)acetate (7b; 70%), mp 142–144 ꢁC;
and methyl 2-(2-(4-chlorophenyl-sulfonyl)ethylsulfonyl)acetate
(7c; 72%), mp 157–159 ꢁC.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

648
V. Padmavathi, B. C. Venkatesh, C. Premakumari, and A. Padmaja
Vol 49
Table 1
Physical data and analytical data for compounds 10 and 12.
Analyses % Calcd. (Found)
Compd. No.
Mp (ꢁC)
Yield (%)
Molecular formula
C
H
N
10a
10b
10c
12a
12b
12c
153–155
135–137
166–168
157–159
150–152
178–180
70, 75,a 95b
72, 78,a 92b
75, 80,a 94b
69, 73,a 94b
68, 76,a 90b
69, 72,a 93b
C12H15NO5S2
C13H17NO5S2
C12H14ClNO5S2
C12H15NO4S3
C13H17NO4S3
C12H14ClNO4S3
45.41–45.48
47.11–47.16
40.97–41.01
43.22–43.29
44.94–44.98
39.18–39.15
4.76–4.78
5.17–5.13
4.01–4.02
4.53–4.50
4.93–4.95
3.84–3.89
4.41–4.47
4.23–4.27
3.98–4.04
4.20–4.25
4.03–4.07
3.81–3.86
aYields in Method B.
bYields in Method C.
Table 2
IR data of compounds 7–12.
IR (KBr) (cm-1)
Compounds
SO2
C = N
C = O
NH
OH
NH2
7a
7b
7c
8a
8b
8c
9a
9b
1143
1138
1132
1141
1136
1139
1137
1134
1140
1129
1135
1129
1130
1126
1134
1137
1138
1135
1336
1330
1328
1325
1330
1337
1330
1324
1335
1332
1340
1329
1341
1339
1333
1330
1338
1345
–
–
–
–
–
–
–
–
–
1575
1584
1570
–
–
–
1560
1550
1565
1735
1729
1730
1645
1639
1643
658
1670
1664
–
–
–
–
–
–
3390
3381
3375
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
3334
3343
3338
3340
3324
3335
–
–
–
–
–
9c
10a
10b
10c
11a
11b
11c
12a
12b
12c
–
–
1650
1645
1647
–
–
–
3410, 3325
3420, 3330
3415, 3310
–
–
–
–
–
–
–
–
N-(2-Hydroxyethyl)-2-(arylsulfonylethylsulfonyl)acetamide (8).
General Procedure. A mixture of methyl 2-(2-(arylsulfonyl)
to get pure N-(2-chloroethyl)-2-(phenylsulfonylethylsulfonyl)
acetamide (9a; 65%), mp 151–153 ꢁC; N-(2-chloroethyl)-2-
(4-methylphenylsulfonylethylsulfonyl)acetamide (9b; 68%),
mp 142–144 ꢁC; and N-(2-chloroethyl)-2-(4-chlorophenylsulfonyle-
thylsulfonyl)-acetamide (9c; 71%), mp 170–172 ꢁC.
ethylsulfonyl)acetate (7; 10 mmol), 2-aminoethanol (10 mmol),
methanol (5 mL), and NaOMe (10 mmol) was refluxed for
6–8 h. The solution was concentrated, cooled, and poured
onto crushed ice. The solid separated was filtered, dried, and
recrystallized from methanol yielded analytically pure
N-(2-hydroxyethyl)-2-(ꢁphenylsulfonylethylsulfonyl)acetamide
(8a; 70%), mp 100–102 C; N-(2-hydroxyethyl)-2-(4-methylphenyl-
sulfonylethylsulfonyl)acetamide (8b; 74%), mp 115–117 ꢁC;
and N-(2-hydroxyethyl)-2-(4-chlorophenylsulfonylethylsulfonyl)
acetamide (8c; 72%), mp 132–134 ꢁC.
2-((2-(Arylsulfonyl)ethylsulfonyl)methyl)-4,5-dihydrooxazole (10).
General Procedure.
To a solution of N-(2-chloroethyl)-2-
(arylsulfonylethylsulfonyl)acetamide (9; 1 mmol) in tetrahydrofuran
(3 mL), a catalytic amount of sodium hydride was added and
refluxed for 4–7 h. The reaction mixture was allowed to attain room
temperature and poured onto crushed ice. The solid obtained was
filtered, dried, and recrystallized from methanol.
N-(2-Chloroethyl)-2-(arylsulfonylethylsulfonyl)acetamide (9).
S-2-Aminoethyl 2-(2-(arylsulfonyl)ethylsulfonyl)ethanethioate
(11). General Procedure. A mixture of methyl 2-(2-(arylsulfonyl)
ethylsulfonyl)acetate (7; 1 mmol), 2-aminoethanethiol (1.5 mmol),
methanol (5 mL), and NaOMe (1 mmol) was refluxed for 3–5 h.
The solution was cooled and poured onto crushed ice. The solid
separated was filtered, dried, and recrystallized from methanol to
General Procedure.
The compound N-(2-hydroxyethyl)-2-
(arylsulfonylethylsulfonyl)acetamide (8; 10 mmol), thionyl
chloride (15 mmol), and methanol (10 mL) were refluxed for
11–13 h. It was cooled and poured onto crushed ice. The solid
separated was filtered, dried, and crystallized from methanol
Journal of Heterocyclic Chemistry
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Synthesis of a New Class of Arylsulfonylethylsulfonylmethyloxazolines and Thiazolines
649
Table 3
31H and 13C NMR data of compounds 6–12.
Compound
1H NMR (d, ppm)
13C NMR (d, ppm)
6a
3.33 (t, 2H, CH2—SO2, J = 4.2 Hz),
3.40 (t, 2H, SO2—CH2, J = 4.2 Hz), 4.42 (s, 2H, CH2—CO),
7.68–8.03 (m, 5H, Ar-H), 13.58 (bs, 1H, OH)
2.35 (s, 3H, Ar-CH3), 3.39 (t, 2H, CH2—SO2, J = 4.0 Hz),
3.46 (t, 2H, SO2—CH2, J = 4.0 Hz), 4.49 (s, 2H, CH2—CO),
7.71–8.05 (m, 4H, Ar-H), 12.71 (bs, 1H, OH)
46.8 (CH2—SO2), 48.1 (SO2—CH2),
57.5 (CH2—CO), 164.9 (CO), 128.4, 130.1,
134.9, 138.4 (aromatic carbons)
23.8 (Ar-CH3), 45.6 (CH2—SO2),
47.2 (SO2—CH2), 58.7 (CH2—CO),
165.2 (CO), 129.2, 131.7, 133.6, 139.5
(aromatic carbons)
6b
6c
7a
3.29 (t, 2H, CH2—SO2, J = 4.3 Hz),
46.1 (CH2—SO2), 47.9 (SO2—CH2),
56.9 (CH2—CO), 163.7 (CO), 128.9,
131.4, 134.1, 137.2 (aromatic carbons)
46.9 (CH2—SO2), 48.6 (SO2—CH2),
53.3 (OCH3), 57.9 (CH2—CO),
162.8 (CO), 128.1, 129.5, 134.3, 138.2
(aromatic carbons)
3.41 (t, 2H, SO2—CH2, J = 4.3 Hz), 4.40 (s, 2H, CH2—CO),
7.52–7.98 (m, 4H, Ar-H), 12.91 (bs, 1H, OH)
3.58 (t, 2H, CH2—SO2, J = 4.0 Hz),
3.68 (t, 2H, SO2—CH2, J = 4.0 Hz), 3.82 (s, 3H, OCH3),
4.05 (s, 2H, CH2—CO), 7.60–7.95 (m, 5H, Ar-H)
7b
7c
8a
8b
2.41 (s, 3H, Ar-CH3), 3.49 (t, 2H, CH2—SO2, J = 4.2 Hz),
3.61 (t, 2H, SO2—CH2, J = 4.2 Hz), 3.79 (s, 3H, OCH3),
4.13 (s, 2H, CH2—CO), 7.66–8.01 (m, 4H, Ar-H)
24.9 (Ar-CH3), 45.4 (CH2—SO2),
47.6 (SO2—CH2), 54.1 (OCH3),
58.6 (CH2—CO), 164.7 (CO), 130.1,
132.0, 134.7, 139.5 (aromatic carbons)
45.7 (CH2—SO2), 47.9 (SO2—CH2),
53.8 (OCH3), 56.4 (CH2—CO),
164.2 (CO), 129.2, 130.5, 134.7,
137.1 (aromatic carbons)
42.2 (NH—CH2), 47.0 (CH2—SO2),
48.2 (SO2—CH2), 58.2 (CH2—CO),
59.8 (CH2—OH), 162.1 (CO-NH), 128.4,
130.1, 134.9, 138.4 (aromatic carbons)
22.9 (ar-CH3), 43.4 (NH—CH2),
47.8 (CH2—SO2), 48.9 (SO2—CH2),
57.3 (CH2—CO), 58.7 (CH2—OH),
164.5 (CO-NH), 129.5, 131.1, 134.2,
139.7 (aromatic carbons)
3.50 (t, 2H, CH2—SO2, J = 4.3 Hz), 3.59 (t, 2H, SO2—CH2, J = 4.3 Hz),
3.80 (s, 3H, OCH3), 4.12 (s, 2H, CH2—CO), 7.58–8.01 (m, 4H, Ar-H)
3.12 (t, 2H, NH—CH2, J = 4.2 Hz), 3.34 (t, 2H, CH2—OH, J = 4.2 Hz),
3.60 (t, 2H, CH2—SO2, J = 4.8 Hz), 3.73 (t, 2H, SO2—CH2, J = 4.8 Hz),
4.22 (s, 2H, CH2—CO), 4.75 (bs, 1H, OH), 7.69–7.94 (m, 5H, Ar-H),
8.39 (bs, 1H, NH)
2.32 (s, 3H, Ar-CH3), 3.24 (t, 2H, NH—CH2, J = 4.3 Hz),
3.38 (t, 2H, CH2—OH, J = 4.3 Hz),
3.56 (t, 2H, CH2—SO2, J = 5.0 Hz), 3.69 (t, 2H, SO2—CH2, J = 5.0 Hz),
4.34 (s, 2H, CH2—CO), 4.81 (bs, 1H, OH),
7.60–8.03 (m, 4H, Ar-H), 8.51 (bs, 1H, NH)
8c
9a
9b
3.19 (t, 2H, NH—CH2, J = 4.1 Hz), 3.32 (t, 2H, CH2—OH, J = 4.1 Hz),
3.56 (t, 2H, CH2—SO2, J = 4.6 Hz), 3.69 (t, 2H, SO2—CH2, J = 4.6 Hz),
4.30 (s, 2H, CH2—CO), 4.68 (bs, 1H, OH),
43.1 (NH—CH2), 47.1 (CH2—SO2),
48.0 (SO2—CH2), 57.8 (CH2—CO),
59.7 (CH2—OH), 163.7 (CO-NH),
7.65–7.99 (m, 4H, Ar-H), 8.43 (bs, 1H, NH)
128.7, 131.3, 133.8, 137.9 (aromatic carbons)
42.1 (NH—CH2), 44.9 (CH2—SO2),
45.8 (CH2—Cl), 47.5 (SO2—CH2),
59.7 (CH2—CO), 163.8 (CO—NH),
129.1, 131.4, 134.4, 137.6 (aromatic carbons).
24.1 (Ar-CH3), 41.0 (NH—CH2),
44.7 (CH2—SO2), 46.1 (CH2—Cl),
48.4 (SO2—CH2), 59.1 (CH2—CO),
164.3 (CO—NH), 130.2, 131.7,
3.28 (t, 2H, NH—CH2, J = 4.4 Hz), 3.60 (t, 2H, CH2—Cl, J = 4.4 Hz),
3.69 (t, 2H, SO2—CH2, J = 5.1 Hz), 3.74 (t, 2H, CH2—SO2, J = 5.1 Hz),
4.31 (s, 2H, CH2—CO), 7.64–7.88 (m, 5H, Ar-H), 8.73 (bs, 1H, NH).
2.41 (s, 3H, Ar-CH3), 3.35 (t, 2H, NH—CH2, J = 4.3 Hz),
3.75 (t, 2H, CH2—Cl, J = 4.3 Hz), 3.79 (t, 2H, CH2—SO2, J = 4.8 Hz),
3.81 (t, 2H, SO2—CH2, J = 4.8 Hz), 4.38 (s, 2H, CH2—CO),
7.70–7.98 (m, 4H, Ar-H), 8.95 (bs, 1H, NH)
134.6, 139.5 (aromatic carbons)
9c
3.32 (t, 2H, NH—CH2, J = 4.5 Hz), 3.54 (t, 2H, CH2—Cl, J = 4.5 Hz),
3.59 (t, 2H, SO2—CH2, J = 5.0 Hz), 3.74 (t, 2H, CH2—SO2, J = 5.0 Hz),
4.34 (s, 2H, CH2—CO), 7.60–7.97 (m, 4H, Ar-H), 8.95 (bs, 1H, NH)
40.6 (NH—CH2), 43.7 (CH2—SO2),
44.5 (CH2—Cl), 46.4 (SO2—CH2),
58.1 (CH2—CO), 165.0 (CO—NH),
128.7, 130.6, 134.1, 138.0 (aromatic carbons)
42.96 (CH2—SO2), 47.31 (SO2—CH2),
50.1 (C-4), 59.3 (CH2—C¼), 62.3 (C-5),
164.6 (C-2), 127.8, 129.6, 134.3,
138.1 (aromatic carbons)
10a
10b
2.82 (t, 2H, C4—H, J = 4.5 Hz), 3.57 (t, 2H, C5—H, J = 4.5 Hz),
3.62 (t, 2H, CH2—SO2, J = 5.2 Hz), 3.67 (t, 2H, SO2—CH2, J = 5.2 Hz),
3.79 (s, 2H, CH2—C¼), 7.66–7.80 (m, 5H, Ar-H)
2.32 (s, 3H, Ar-CH3), 2.85 (t, 2H, C4—H, J = 4.3 Hz),
3.50 (t, 2H, C5—H, J = 4.3 Hz), 3.69 (t, 2H, CH2—SO2, J = 5.0 Hz),
3.73 (t, 2H, SO2—CH2, J = 5.0 Hz),
3.80 (s, 2H, CH2—C¼), 7.56–7.99 (m, 4H, Ar-H)
22.9 (Ar-CH3), 43.8 (CH2—SO2),
47.4 (SO2—CH2), 51.5 (C-4),
59.8 (CH2—C¼), 63.1 (C-5),
163.8 (C-2), 128.2, 130.0, 133.9,
138.5 (aromatic carbons)
10c
2.79 (t, 2H, C4—H, J = 4.4 Hz),
3.52 (t, 2H, C5—H, J = 4.4 Hz), 3.67 (t, 2H, CH2—SO2, J = 4.9 Hz),
3.70 (t, 2H, SO2—CH2, J = 4.9 Hz),
3.81 (s, 2H, CH2—C¼), 7.60–7.92 (m, 4H, Ar-H)
43.0 (CH2—SO2), 46.9 (SO2—CH2),
50.8 (C-4), 58.9 (CH2—C¼), 63.4 (C-5),
163.5 (C-2), 128.1, 129.3, 133.8,
137.8 (aromatic carbons)
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

650
V. Padmavathi, B. C. Venkatesh, C. Premakumari, and A. Padmaja
Vol 49
Table 3
(Continued)
Compound
1H NMR (d, ppm)
13C NMR (d, ppm)
11a
3.25 (t, 2H, S—CH2, J = 4.1 Hz), 3.35 (t, 2H, CH2—NH2, J = 4.1 Hz),
3.65 (t, 2H, CH2—SO2, J = 5.8 Hz), 3.78 (t, 2H, SO2—CH2, J = 5.8 Hz),
4.30 (s, 2H, CH2—CO), 5.48 (s, 2H, NH2), 7.59–7.98 (m, 5H, Ar-H)
38.5 (CH2—NH2), 41.7 (S—CH2),
45.8 (SO2—CH2), 47.6 (CH2—SO2),
59.4 (CH2—CO), 182.3 (CO), 129.5,
131.6, 134.2, 137.4 (aromatic carbons)
23.9 (Ar-CH3), 37.9 (CH2—NH2),
42.4 (S—CH2), 46.7 (SO2—CH2),
47.9 (CH2—SO2), 58.9 (CH2—CO),
181.3 (CO), 128.2, 130.7, 134.8,
139.1 (aromatic carbons)
11b
2.38 (s, 3H, Ar-CH3), 3.31 (t, 2H, S—CH2, J = 4.5 Hz),
3.40 (t, 2H, CH2—NH2, J = 4.5 Hz), 3.60 (t, 2H, CH2—SO2, J = 6.0 Hz),
3.72 (t, 2H, SO2—CH2, J = 6.0 Hz), 4.37 (s, 2H, CH2—CO),
5.39 (s, 2H, NH2), 7.69–8.05 (m, 4H, Ar-H)
11c
12a
12b
12c
3.36 (t, 2H, S—CH2, J = 4.3 Hz),
3.38 (t, 2H, CH2—NH2, J = 4.3 Hz),
3.66 (t, 2H, CH2—SO2, J = 5.6 Hz), 3.76 (t, 2H, SO2—CH2, J = 5.6 Hz),
4.41 (s, 2H, CH2—CO), 5.46 (s, 2H, NH2),
7.62–8.01 (m, 4H, Ar-H)
2.91 (t, 2H, C4—H, J = 4.4 Hz), 3.10 (t, 2H, C5—H, J = 4.4 Hz),
3.65 (t, 2H, CH2—SO2, J = 5.9 Hz), 3.70 (t, 2H, SO2—CH2, J = 5.9 Hz),
3.81 (s, 2H, CH2—C¼), 7.60–7.91 (m, 5H, Ar-H)
37.8 (CH2—NH2), 42.4 (S—CH2),
45.1 (SO2—CH2), 48.2 (CH2—SO2),
58.4 (CH2—CO), 182.7 (CO),
128.1, 131.0, 134.9, 138.0
(aromatic carbons)
38.1 (C-5), 46.3 (CH2—SO2),
47.1 (so2—CH2), 52.4 (C-4),
58.7 (CH2—C¼), 162.9 (C-2),
129.1, 130.6, 134.8, 137.3
(aromatic carbons)
24.5 (Ar-CH3), 37.8 (C-5),
2.29 (s, 3H, Ar-CH3), 2.86 (t, 2H, C4—H, J = 4.6 Hz),
3.18 (t, 2H, C5—H, J = 4.6 Hz), 3.59 (t, 2H, CH2—SO2, J = 5.5 Hz),
3.68 (t, 2H, SO2—CH2, J = 5.5 Hz), 3.85 (s, 2H, CH2—C¼),
7.67–8.07 (m, 4H, Ar-H)
46.9 (CH2—SO2), 47.6 (so2—CH2),
53.0 (C-4), 59.1 (CH2—C¼), 163.7 (C-2),
128.1, 131.4, 134.0, 139.7
(aromatic carbons)
38.7 (C-5), 47.0 (CH2—SO2),
48.1 (so2—CH2), 52.8 (C-4),
58.4 (CH2—C¼), 164.5 (C-2),
129.7, 130.9, 133.7, 138.5
(aromatic carbons)
2.90 (t, 2H, C4—H, J = 4.2 Hz), 3.15 (t, 2H, C5—H, J = 4.2 Hz),
3.59 (t, 2H, CH2—SO2, J = 5.7 Hz), 3.76 (t, 2H, SO2—CH2, J = 5.7 Hz),
3.84 (s, 2H, CH2—C¼), 7.55–8.03 (m, 4H, Ar-H)
obtain pure S-2-aminoethyl 2-(2-(phenylsulfonyl)ethylsulfonyl)-
2-((2-(Arylsulfonyl)ethylsulfonyl)methyl)-4,5-dihydrothiazole (12).
General procedure. To a flask charged with anhydrous samarium
ꢁ
ethanethioate (11a; 66%), mp120–122 C; S-2-aminoethyl 2-(2-
ꢁ
tosylethylsulfonyl) ethanethioate (11b; 69%), mp 116–118 C;
(III) chloride (0.1 mmol) and dry toluene (10 mL), 2-aminoethanethiol
and S-2-aminoethyl 2-(2-(4-chlorophenylsulfonyl)ethylsulfonyl)-
(2 mmol) was added followed by n-butyllithium (2.2 mmol) at 0 ꢁC.
ethanethioate (11c; 65%), mp 126–128 ꢁC.
ꢁ
The reaction mixture was stirred at 0 C for 30 min and heated to
2-((2-(Arylsulfonyl)ethylsulfonyl)methyl)-4,5-dihydrothiazole
(12). General procedure. To a solution of S-2-aminoethyl 2-(2-
(phenylsulfonyl)ethylsulfonyl)-ethanethioate (11; 2 mmol) in
tetrahydrofuran (6 mL), a catalytic amount of sodium hydride
was added and refluxed for 7–10 h. The reaction mixture was
concentrated, cooled, and poured onto crushed ice. The solid
obtained was filtered, dried, and recrystallized from methanol.
reflux. Then, methyl 2-(2-(arylsulfonyl)ethylsulfonyl)acetate (7; 1
mmol) was added to the contents and continued refluxion for an
additional period of 6–9 h. The suspension was cooled to room
temperature and filtered. The filtrate was extracted with chloroform,
washed with water followed by brine solution. The solvent was
removed in vacuo. The solid obtained was purified by column
One-pot methodology for synthesis of 2-oxazolines and 2-
thiazolines by using Samarium (III) chloride (Method B).
2-((2-(Arylsulfonyl)ethylsulfonyl)methyl)-4,5-dihydrooxazole (10).
chromatography (silica gel, ethyl acetate:hexane, 1:3).
One-pot methodology for the synthesis of 2-oxazolines
and 2-thiazolines under microwave irradiation (Method C).
2-((2-(Arylsulfonyl)ethylsulfonyl)methyl)-4,5-dihydrooxazole (10).
General procedure.
To a flask charged with anhydrous
samarium (III) chloride (0.1 mmol) and dry toluene (10 mL),
General procedure.
A mixture of 2-(2-(arylsulfonyl)ethylsulfonyl)
2-aminoethanol (2 mmol) was added followed by n-butyllithium (2.2
acetic acid (6; 10 mmol) and 2-aminoethanol (10 mmol) were placed
in a Pyrex flask in such a way as to occupy only 10% of the overall
volume. The mixture was irradiated using the multimode at 540 watts
for 3 min and monitored by TLC. When all the starting material
had disappeared, the irradiation was terminated, and the mixture
was brought to room temperature. To this, dichloromethane was
added and filtered. The resultant compound obtained by
evaporation of the solvent under reduced pressure was purified by
column chromatography (silica gel, ethyl acetate:hexane, 1:2.5).
ꢁ
mmol) at 0 C. The reaction mixture was stirred at 0 ꢁC for 30min
and heated to reflux. Then, methyl 2-(2-(arylsulfonyl)ethylsulfonyl)
acetate (7; 1 mmol) was added to the contents and continued
refluxion for an additional period of 6–9 h. The suspension was
cooled to room temperature and filtered. The filtrate was extracted
with chloroform, washed with water followed by brine solution. The
solvent was removed in vacuo. The solid obtained was purified by
column chromatography (silica gel, ethyl acetate:hexane, 1:3).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2012
Synthesis of a New Class of Arylsulfonylethylsulfonylmethyloxazolines and Thiazolines
651
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2-((2-(Arylsulfonyl)ethylsulfonyl)methyl)-4,5-dihydrothiazole
(12). General procedure.
The compound 2-(2-(arylsulfonyl)
ethylsulfonyl)acetic acid (6; 10 mmol) and 2-aminoethanethiol
(10 mmol) were placed in a Pyrex flask in such a way as to
occupy only 10% of the overall volume. The mixture was
irradiated at 560 watts for 4 min and monitored by TLC. When
all the starting material had disappeared, the irradiation was
terminated, and the mixture was allowed to cool to room
temperature. The dichloromethane was added to the resulting
mixture and filtered. The compound obtained after evaporation
of the solvent under vacuum was purified by column
chromatography (silica gel, ethyl acetate:hexane, 1:2.5).
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Acknowledgments. The authors thank University Grants Com-
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project.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet