4
608
M. Kumar et al. / Tetrahedron Letters 53 (2012) 4604–4608
(
B) by acidification with sulfuric acid (Scheme 1). The ionic liquid was obtained
in quantitative yield with high purity.
(
a) Preparation of 1-alkyl-3-(butyl-4-sulfonate) imidazolium salt (A): 1-
Methylimidazole (10.0 g, 1.2 mol) and 1,4-butane sultone (16.6 g, 1.2 mol)
were vigorously stirred overnight at 70 °C in dry toluene (80 mL). The white
precipitate was filtered off, thoroughly washed with diethyl ether and finally
1
dried in vacuum. Spectroscopic data for (A): Mp 233–235 °C.
H NMR
(
3
300 MHz, DMSO-d
6
, TMS); 1.54 (m, 2H), 1.87 (m, 2H), 2.6 (t, 2H,), 3.79 (s,
13
H), 4.20 (t, 2H), 7.32 (s, 1H), 7.4 (s, 1H), 9.27 (s, 1H), 11.60 (bs, 2H). C NMR
(
75 MHz, DMSO-d
6
, TMS); 22.09, 28.17, 36.34, 48.96, 51.88, 123.06, 124.28,
138.03.
(
b) Preparation of SO
3 2 4 3 4
H-functionalized ionic liquid ([MIM(CH ) SO H][HSO ])
(
B): Stoichiometric amount of sulfuric acid was added to the zwitterions A and
the mixture was stirred at 80 °C for 7 h to obtain the ionic liquid. The ionic
liquids BmimPF and BmimBF have also been prepared according to the
method reported in literature.
6
4
1
2
23. Representative procedure: A dry 25 ml round bottomed flask was charged with
substituted 2-aminobenzothiazole (1 mmol), isatin (1 mmol), two different
2
1,3-dicarbonyl compounds (1 mmol each) and [SFIL] (1.0 ml)/H O (1.0 ml). The
mixture solution was heated at 80 °C, under magnetic stirring, for 15 min. The
progress of the reaction was monitored by TLC. After completion of the
reaction, the reaction mixture was cooled to room temperature and filtered to
afford the crude product, which was washed and purified by recrystallization
from ethanol. The ionic liquid was recovered from the aqueous solution by
evaporating under reduced pressure and reused in the next cycle.
2 4 3 4
Figure 1. Reusability of ([MIM(CH ) SO H][HSO ]).
spiroheterocycles with fused heterosystems in excellent yields
using a halogenfree SO H-functionalized ionic liquid/water as
recyclable medium. To the best of our knowledge the synthesis
of spiroheterocycles with such fused heterosystems in SO H-func-
3
1
0-(6-Methylbenzothiazol-2-yl)-1,3,8,8-tetramethyl-1H,3H-8,9-dihydro-7H-
spiro[pyrimido[4,5-b]quinoline-5,3 -indoline]-2,2 ,4,6-tetrone (7c) Mp 221–
223 °C, IR (KBr): 3210, 1740, 1700 and 620 cm
ppm): 0.99 (3H, s, CH ), 1.08 (3H, s, CH ), 2.07–2.15 (2H, m, CH
CH ), 2.45–2.60 (2H, m, CH ), 3.01 (3H, s, CH ), 3.45 (3H, s, CH ), 6.86–7.43 (7H,
m, H-Ar), 10.95 (1H, s, NH). C NMR (DMSO-d ) d (ppm) : 19.3, 20.9, 25.7, 26.6,
28.3, 30.2, 45.8, 47.3, 53.1, 79.9, 108.5, 120.8, 122.0, 122.9, 123.6, 124.3, 125.1,
27.1, 130.5, 135.5, 142.4, 144.6, 145.1, 153.5, 167.9, 170.0, 174.1, 197.2.
0
0
ꢀ
1
1
.
H NMR (DMSO-d
6
) d
3
(
3
3
2
), 2.41 (3H, s,
tionalized ionic liquid/water system has not been documented in
the literature. The advantages of this synthetic protocol are mild
reaction conditions, shorter reaction times, easy work-up, excel-
lent yields, and recycled and reusable solvent/catalyst.
3
2
13
3
3
6
1
+
HRMS-FAB: m/z Calcd for [M+H] 553.1784. Found: 553.1779. Anal. Calcd (%)
for C30 S: C 65.08, H 4.92, N 12.65. Found: C 65.01, H 5.01, N 12.59.
12-(6-Bromo-4-methylbenzothiazol-2-yl)-2-methylspiro[chromeno[3,4-b]pyr
27 5 4
H N O
References and notes
0
0
ano-pyridine-5,3 -indoline]-2 ,4,6-trione (8a) Mp 218–221 °C, IR (KBr): 3285,
ꢀ
1 1
3
210, 3190, 1700, 1650 and 1610 cm
s, CH ), 2.49 (3H, s, CH ), 6.75–7.92 (11H, m, HAr), 10.43 (1H, s, NH). C NMR
DMSO-d ) d (ppm): 15.3, 18.5, 38.6, 38.9, 39.2, 39.7, 40.0, 40.3, 50.7, 53.4, 56.0,
09.4, 119.0, 120.9, 121.4, 124.7, 128.0, 128.7, 128.9, 130.2, 143.1, 150.1, 151.6,
. H NMR (DMSO-d ) d (ppm): 2.22 (3H,
6
1
2
3
.
.
.
Anastas, P.; Eghbali, N. Chem. Soc. Rev. 2010, 39, 301.
13
Nielsen, T. E.; Schreiber, S. L. Angew. Chem., Int. Ed. 2008, 47, 48.
Coquerel, Y.; Boddaert, T.; Presset, M.; Mailhol, D.; Rodriguez, J. In Ideas in
Chemistry and Molecular Sciences Advances in Synthetic Chemistry; Pignataro, B.,
Ed.; Wiley-VCH: Weinheim, Germany, 2010; pp 187–202. Chpter 9.
Sapi, J.; Laronze, J. Y. Arkivoc 2004, 7, 208.
(a) Zhu, J.; Bienaym e´ , H. Multicomponent Reactions; Wiley-VCH: Weinheim,
Germany, 2005; (b) Isambert, N.; Lavilla, R. Chem. Eur. J. 2008, 14, 8444.
Hallet, J. P.; Welton, T. Chem. Rev. 2011, 111, 3508.
Holbrey, J. D.; Reichert, W. M.; Swatloski, R. P.; Broker, G. A.; Pitner, R. W.;
Seddon, K. R.; Rogers, R. D. Green Chem. 2002, 4, 407.
Arya, A. K.; Kumar, M. Green Chem. 2011, 13, 1332.
Arya, A. K.; Kumar, M. Mol. Divers. 2011, 15, 781.
0. Kumar, M.; Sharma, K.; Samarth, R. M.; Kumar, A. Eur. J. Med. Chem. 2010, 45,
467.
3
3
(
6
1
1
6
1
53.0, 167.2, 167.6, 175.6. Anal. Calcd (%) for C31
.73. Found: C 59.61, H 2.89, N 6.77.
3 5
H18BrN O S: C 59.62, H 2.91, N
4
5
.
.
2-(6-Bromo-4-methylbenzothiazol-2-yl)-2,2-dimethyl-2,3-dihydro-1H-spiro
0 0
chromeno [3,4-b]quinoline-5,3 -indoline]-2 ,4,6-trione (9a) Mp 212–217 °C,
1 1
[
ꢀ
IR (KBr): 3285, 3210, 3190, 1700, 1650 and 1610 cm
.
H NMR (DMSO-d
), 3.02 (3H, s,
), 6.69–7.59 (10H, m, H-Ar), 11.16 (1H, s, NH). C NMR (DMSO-d ) d
ppm): 18.3, 28.2, 28.3, 38.6, 38.9, 39.2, 39.7, 40.0, 40.3, 51.7, 54.2, 109.2,
6
) d
6
7
.
.
(
CH
(
ppm): 0.99 (3H, s, CH
3
), 1.07 (3H, s, CH ), 2.09–2.32 (4H, m, CH
3
2
13
3
6
8
9
1
.
.
1
1
20.6, 120.9, 124.9, 129.0, 137.7, 138.9, 139.6, 143.0, 148.7, 151.1, 165.7,
68.0, 175.7, 196.1. Anal. Calcd (%) for C33 24BrN S: C 62.07, H 3.79, N 6.58.
H
3 4
O
Found: C 62.10, H 3.81, N 6.57.
0-(6-Bromo-4-methylbenzothiazol-2-yl)-2,8,8-trimethyl-8,9-dihydro-7H-
4
1
1
1. Gupta, R. R.; Kumar, M. Synthesis, Reactions and Properties of Phenothiazines’ in:
Phenothiazines and 1,4-Benzothiazines. Chemical and Biomedical Aspect; Elsevier:
Amsterdam, 1988.
2. Rathor, B. S.; Kumar, M. Bioorg. Med. Chem. 2006, 14, 5678.
3. (a) Rathor, B. S.; Gupta, V.; Gupta, R. R.; Kumar, M. Heteroat. Chem. 2007, 18, 81;
0
0
spiro[pyrano [3,4-b]quinoline-5,3 -indoline]-2 ,4,6-trione (10a) Mp 223–
ꢀ
1
1
2
(
CH
26 °C, IR (KBr): 3285, 3210, 3190, 1700, 1650 and 1610 cm
DMSO-d ) d (ppm) : 1.06 (3H, s, CH ), 1.24 (3H, s, CH ), 3.08–3.12 (4H, m,
), 3.37 (3H, s, CH ), 3.71 (3H, s, CH ), 6.74–7.62 (7H, m, H-Ar), 10.6 (1H,
) d (ppm): 20.9, 27.7, 28.2, 38.7, 38.9, 39.2, 39.8,
0.0, 40.3, 51.8, 101.1, 102.3, 109.3, 120.8, 121.5, 125.0, 126.0, 133.7, 137.8,
. H NMR
1
1
6
3
3
2
3
3
1
3
s, NH). C NMR (DMSO-d
6
(
b) Kumar, M.; Sharma, K.; Sharma, D. K. Org. Med. Chem. Lett. 2012, 2, 10.
4
1
5
1
1
1
1
1
4. Hilton, S. T.; Ho, T. C.; Pljevalijcic, G.; Jones, K. Org. Lett. 2000, 17, 2639.
5. Baran, S. P.; Richter, R. M. J. Am. Chem. Soc. 2005, 127, 15394.
6. Xia, M.; Lu, Y. Synlett 2005, 15, 2357.
7. (a) Koruznjak, J. D.; Slade, N.; Zamola Pavelic, K.; Karminski-Zamola, G. Chem.
Pharm. Bull. 2002, 50, 656; (b) Magedov, I. V.; Manpadi, M.; Ogasawara, M. A.;
Dhawan, A. S.; Rogelj, S.; Slambrouck, S. V.; Stlleelant, W. F. A.; Evdokimov, N.
M.; Uglinskii, P. Y.; Elias, E. M.; Knee, E. J.; Tongwa, P.; Antipin, M. Y.;
Kornienko, A. J. Med. Chem. 2008, 51, 2561; (c) Deb, M. L.; Bhuyan, P. J. Beilst J.
Org. Chem. 2010, 6, 11.
8. Bharate, S. B.; Bhutani, K. K.; Khan, S. I.; Tekwani, B. L.; Jacob, M. R.; Khan, I. A.;
Singh, I. P. Bioorg. Med. Chem. 2006, 14, 1750.
9. (a) Henriksen, G.; Yousefi, B. H.; Drzezga, A.; Wester, H. J. Eur. J. Nucl. Med. Mol.
Imaging. 2008, 35, 75; (b) Yoshida, M.; Hayakawa, I.; Hayashi, N.; Agatsuma, T.;
Oda, Y.; Tanzawa, F.; Iwasaki, S.; Koyama, K.; Furukaw, H.; Kurakata, S. Bioorg.
Med. Chem. Lett. 2005, 15, 3328.
38.6, 161.1, 165.8, 180.7, 196.7. Anal. Calcd (%) for C30
9.80, H 4.02, N 6.97. Found: C 59.25, H 4.12, N 6.90.
2-(6-Bromo-4-methylbenzothiazol-2-yl)-1,3-dimethyl-1H,3H-spiro[chro
3 4
H24BrN O S: C
0
meno[3,4-b]pyrido[2,3-d]pyrimidine-indoline]-2,2 ,4,6-tetrone (11a) Mp
ꢀ
1
1
2
(
20–224 °C, IR (KBr): 3285, 1732, 1710, 1670 and 1630 cm
DMSO-d ) d (ppm): 2.48 (3H, s, CH ), 3.08 (3H, s, CH ), 3.50 (3H, s, CH
.68–8.07 (10H, m, H-Ar), 10.6 (1H, s, NH). C NMR (DMSO-d ) d (ppm):
.
H NMR
6
3
3
3
),
1
3
6
2
1
1
5
1
6
0.9, 38.6, 38.9, 39.2, 39.7, 40.0, 40.3, 78.2, 100.8, 109.7, 115.6, 116.1, 120.8,
21.6, 123.1, 123.8, 124.3, 126.8, 129.8, 130.7, 132.8, 137.8, 138.6, 142.9,
52.1, 159.4, 164.8, 175.4, 180.7. Anal. Calcd (%) for C31
6.89, H 3.08, N 10.70. Found: C 56.91, H 3.11, N 10.68.
1
5 5
H20BrN O S: C
1
0-(6-Bromo-4-methylbenzothiazol-2-yl)-1,3,8-trimethyl-1H,3H-spiro[pyr
0
ano[3,4-b]pyrido[2,3-d]pyrimidine-indoline]-2,2 ,4,6-tetrone (12a) Mp
2
18–221 °C, IR (KBr): 3285, 3210, 3190, 1700, 1650 and 1610 cmꢀ1. 1
NMR (DMSO-d ) d (ppm): 3.01 (3H, s, CH ), 3.06 (3H, s, CH ), 3.12 (3H, s,
CH ), 3.36 (3H, s, CH ), 6.81–7.79 (7H, m, H-Ar), 10.55 (1H, s, NH). C NMR
DMSO-d ) d (ppm): 19.0, 20.9, 38.6, 38.9, 39.2, 39.7, 40.0, 40.3, 77.4, 98.3,
00.9, 109.5, 120.8, 121.5, 123.5, 126.0, 129.5, 131.0, 137.8, 138.6, 142.7,
H
2
2
0. Solomon, V. R.; Hu, C.; Lee, H. Bioorg. Med. Chem. 2009, 17, 7585.
1. Palanikumar, S. S.; Siddiqui, S. A.; Thomas, D.; Lahoti, R. J.; Srinivasan, K. V. Org.
Chem. 2003, 68, 9371.
2. Preparation of ionic liquids: The method involves the reaction of 1-
methylimidazole with 1,4-butane sultone in equimolar ratio to afford the
6
3
3
1
3
3
3
(
6
1
1
5
2
61.6, 162.0, 169.0, 175.6, 180.7. Anal. Calcd (%) for C28
4.38, H 3.26, N 11.32. Found: C 54.41, H 3.25, N 11.35.
5 5
H20BrN O S: C
3
zwitterions (A) that is further converted into SO H-functionalised ionic liquid