KF-alumina-mediated Bargellini reaction

Article abstract of DOI:10.1016/j.tetlet.2010.07.029

KF-alumina was found to be an efficient base for the synthesis of sterically hindered α-substituted carboxylic acids. A series of Bargellini reactions were performed by using various substituted anilines, phenols, and thiophenols as nucleophiles with keto

Full text of DOI:10.1016/j.tetlet.2010.07.029

Tetrahedron Letters 51 (2010) 4772–4775
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Tetrahedron Letters
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KF-alumina-mediated Bargellini reaction
*
Md. Rumum Rohman, Bekington Myrboh
Department of Chemistry, North-Eastern Hill University, Mawlai-Mawkynroh, Shillong 793 022, India
a r t i c l e i n f o
a b s t r a c t
Article history:
KF-alumina was found to be an efficient base for the synthesis of sterically hindered a-substituted car-
Received 13 April 2010
Revised 2 July 2010
Accepted 6 July 2010
Available online 8 July 2010
boxylic acids. A series of Bargellini reactions were performed by using various substituted anilines, phe-
nols, and thiophenols as nucleophiles with ketones in the presence of chloroform and KF-alumina as a
base. All the compounds were fully characterized.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Bargellini reaction
KF-alumina
Nucleophile
Bargellini reaction provides a multi component, atom efficient
synthesis of molecules with significantly increased complexity,
diversity, and functionality. The condensation of phenols with
chloroform and acetone in the presence of sodium hydroxide to
reaction,6c the Wittig reaction,6d the Biginelli reaction,7 alkylation,8
and elimination reaction.9 Therefore, we decided to use KF/Al2O3 as
a base and/or a source for the ÀOH ion in the Bargellini reaction in
combination with chloroform as a source of carbon for the incorpo-
ration of the carboxylic group.
give
a
-phenoxyisobutyric acids was first reported by Bargellini.1
The application of Bargellini reaction includes the preparation of
griseofulvin analogs by Korger.2a Recently, Butcher and Hurst re-
ported an important extension of the Bargellini reaction for the
synthesis of drugs in the pharmaceutical industry.2b
Herein, we report on a convenient KF/Al2O3-promoted Bargel-
lini reaction from cyclic ketones and various nucleophiles such as
substituted aniline, phenols, and thiophenols under mild reaction
conditions (Scheme 1).
Although, there are number of methods reported for the Bargel-
lini reaction using different nucleophiles other than phenols, for
example, (i) potassium amide and sodium azide,3 (ii) aromatic
amines as nucleophile,2b however, in all these reported methods
either sodium or potassium hydroxide was used as a base. To our
knowledge there is no method reported with an alternative base.
Therefore, there is still scope for the development of a better alter-
native method which might proceed under mild, environmentally
benign, and clean reaction condition.
In recent years, the use of inorganic solid-supported regents has
become popular due to their characteristic properties such as en-
hanced reactivity and selectivity, a straight forward work-up pro-
cedure and milder reaction conditions.4 Among these inorganic
solid supports, potassium fluoride coated with alumina (KF/
Al2O3) has been used extensively because of its easy accessibility
and strong basic nature. KF/Al2O3 derives its basicity from the for-
mation of KOH in the initial preparation of the solid-supported
material by the reaction of KF with alumina support.5 Some of
the reported reactions which use the KF/Al2O3 combination include
the Knoevenagel condensation,6a the Henry reaction,6b the Darzens
In the preliminary experiment, the reaction of 1a with chloro-
form in the presence of KF/Al2O3 in ethanol proceeded slow and
afforded the product in a very low yield, while the reaction in tol-
uene led to the formation of the desired compound 3a in high
yield. For example, when 3-chloroaniline (1a) (2 mmol) was trea-
ted with cyclohexanone (2a) (6 mmol) in the presence of chloro-
form (8 mmol) and KF/Al2O3 (6 g, 40% KF in Al2O3) as a base in
dry toluene, 3a was obtained in 91% yield. A number of substituted
aromatic anilines (1b–f) were reacted with cyclohexanone to dem-
onstrate the generality of the reaction in presence of KF/Al2O3. Sim-
ilarly, the reaction of nucleophile 1a with the N-tbutyloxycarbonyl-
protected piperidone (2g) in the presence of KF/Al2O3 underwent
smoothly in 12 h giving product 3g with a very high purity. The
O
O
X
X
KF/Al2O3, CHCl3
Toluene, rt.
OH
R
R
+
Y
Y
1
2
3
X = NH2, OH, SH
Y = CH2, NBoc
* Corresponding author. Tel.: +91 364 2722612; fax: +91 364 2228213.
E-mail address: bmyrboh@nehu.ac.in (B. Myrboh).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.029

M. R. Rohman, B. Myrboh / Tetrahedron Letters 51 (2010) 4772–4775
4773
Table 1
KF/Al2O3 assisted Bargellini reaction of anilines, phenols, thiophenols via Scheme 1
Entry
Substrate 1
Substrate 2
Product 3b
Yielda (%)
Cl
O
O
H
N
O
Cl
a
91
65
56
58
90
OH
OH
OH
NH2
NH2
H
N
Br
b
c
2a
2a
2a
2a
Br
O
O
O
H
N
NH2
NO2
NH2
O
NO
2 H
N
d
e
OH
O
H
N
NH2
NH2
OH
Cl
Cl
Cl
O
H
N
OH
O
f
2a
78
72
Cl
H
N
Boc N
O
Cl
OH
OH
g
1a
N
Boc
O
H
N
h
i
1b
1c
1e
2g
2g
58
60
Br
N
Boc
O
O
H
N
OH
N
Boc
O
H
N
OH
j
2g
2a
2g
73
68
75
N
Boc
O
OH
N
H
N
NH2
N
N
k
l
O
H
N
OH
1k
N
Boc
O
OH
O
m
n
2a
2a
2a
67c
75c
OH
Cl
Cl
O
O
OH
SH
OH
Cl
Cl
O
S
o
73
OH
(continued on next page)

4774
M. R. Rohman, B. Myrboh / Tetrahedron Letters 51 (2010) 4772–4775
Table 1 (continued)
Entry
Substrate 1
Substrate 2
Product 3b
Yielda (%)
80
O
O
Cl
SH
S
S
OH
OH
p
q
2a
Cl
Cl
1p
2g
65
N
Boc
a
Isolated yields.
b
Products have been characterized by recording IR, 1H NMR and 13C NMR.
THF as a solvent.
c
3. (a) Reeve, W. Synthesis 1971, 131; (b) Corey, E. J.; Link, J. O. J. Am. Chem. Soc.
1992, 114, 1906.
present procedure was then employed for the condensation of var-
ious substituted anilines (entries 1h–j, Table 1) and N-tbutyloxy-
carbonyl-protected piperidone (2g) to give the corresponding
Bargellini compounds (3h–j) in good to excellent yields.
4. (a) Bunin, B. A. The Combinatorial Index; Academic: New York, 1998; (b) Czarnik,
A. W.; DeWitt, S. H. A Practical Guide to Combinatorial Chemistry; American
Chemical Society: Washington, DC, 1997; (c) Nicolaou, K. C.; Hanko, R.;
Hartwig, W. Handbook of Combinatorial Chemistry; Wiley-VCH: Weinheim,
2002.
5. Blass, B. E. Tetrahedron 2002, 58, 9301. and the references cited therein.
6. (a) Thompson, A. M.; Bridges, A. J.; Fry, D. W.; Kraker, A. J.; Denny, W. A. J. Med.
Chem. 1995, 38, 3780; (b) Bredereck, H.; Gompper, R.; Schuh, H. G.; Theilig, G.
Angew. Chem. 1959, 71, 753; (c) Monge, A.; Martinez-Merino, V.; Sanmartin, C.;
Fernandez, F. J.; Ochoa, M. C.; Bellver, C.; Artigas, P.; Fernandez-Alvarez, E. Eur.
J. Med. Chem. 1989, 24, 209; (d) Matsunaga, T.; Tohda, Y.; Ariga, M. J. Chem. Soc.,
Perkin Trans. 1 2000, 27.
In order to test the scope of KF/Al2O3 base, we treated heterocy-
clic nucleophile 2-aminopyridine (1k) with 2a and 2g, which suc-
cessfully resulted in the formation of compound 3k and 3l in 68%
and 75% yield, respectively. Furthermore, this method is extended
to phenols and thiophenols (1m–q) to furnish the desired products
(3m–q) and the results are summarized in Table 1.11 It may be
noted that the reactions of substrates 1m and 1n with compound
2a afforded the products 3m and 3n, respectively, in poor yields
in dry toluene whereas the same reactions in tetrahydrofuran as
solvent afforded 3m and 3n in good yields. This may be due to
the insolubility of the starting phenols (1m–n). All the products
were confirmed by IR, 1H, and 13C NMR spectral studies (Table
1).12 It is important to highlight that the compounds 3m–n were
obtained from 1m–n in 67% and 75% yield, respectively, while
the substituted phenols were reported to give low yields with 2a
and 2g by using NaOH base thus indicating that the present proto-
col is much more effective.2b
It is noteworthy to mention that there is no side reaction ob-
served for the nucleophile having the keto group (entries c and
i); also the use of KF/Al2O3 as a base is tolerated in the presence
of other functional groups while the protecting group N-tbutyloxy-
carbonyl is not affected under the experimental conditions.
Although the mechanistic details remain ambiguous, the KF/
Al2O3-promoted reaction might proceed through deprotonation
of chloroform followed by nucleophilic attack on the ketone yield-
ing dichloro epoxide. The N–C bond is formed via the opening of
dichloro epoxide by the nucleophile to give an acid chloride. Sub-
sequently, the hydrolysis of the acid chloride would lead to the for-
mation of the desired compound.
7. (a) Svetlık, J.; Veizerova, L.; Kettmann, V. Tetrahedron Lett. 2008, 49, 3520; (b)
Suzuki, I.; Iwata, Y.; Takeda, K. Tetrahedron Lett. 2008, 49, 3238.
8. (a) Trapini, G.; Franco, M.; Latrofa, A.; Ricciardi, L.; Carotti, A.; Serra, M.; Sanna,
E.; Biggio, G.; Liso, G. J. Med. Chem. 1999, 42, 3934; (b) Lober, S.; Hubner, H.;
Gmeneir, P. Bioorg. Med. Chem. Lett. 1999, 42, 3934; (c) Rival, Y.; Grassy, G.;
Michel, G. Chem. Pharm. Bull. 1992, 40, 1170; (d) Lyon, M.; Kercker, T. Org. Lett.
2004, 26, 4989; (e) Jaramillo, C.; Carretero, C.; de Diego, E.; Hamoduchi, C.; del
Prado, M.; Roldan, J. L.; Sanchez-Martinez, C. Tetrahedron Lett. 2002, 43, 9051;
(f) Kaminski, J. J.; Wallmark, B.; Briving, C.; Andersson, B. M. J. Med. Chem. 1991,
34, 533; (g) Georges, G.; Vercauteren, D. P.; Vanderveken, D. J.; Horion, R.;
Evrard, G. H.; Durant, F. V.; George, P.; Wick, A. Eur. J. Med. Chem. 1993, 28, 323.
9. (a) Bristow, N. W.; Charlton, P. T.; Peak, D. A.; Short, W. F. J. Chem. Soc. 1954,
616; (b) Tadeka, K.; Shudo, K.; Okamoto, T.; Kousuge, T. Chem. Pharm. Bull.
1978, 26, 2924; (c) Knott, E. B. J. Chem. Soc. 1956, 1360; (d) Sugiura, S.; Akoi, H.
K.; Inouf, S.; Goto, T. Yakukagaku Zasshi 1970, 90, 436; (e) Saint-Ruf, G.;
Loukakou, B.; Zousi, C. J. Heterocycl. Chem. 1981, 18, 1565; (f) Ohta, M.; Masaki,
M. Bull. Chem. Soc. Jpn. 1960, 37, 1392.
10. Henriksen, G.; Platzer, S.; Marton, J.; Hauser, A.; Berthele, A.; Schwaiger, M.;
Marinelli, L.; Lavecchia, A.; Novellino, E.; Wester, H.-J. J. Med. Chem. 2005, 48,
7720.
11. General experimental procedure: To a solution of nucleophiles (2 mmol) in dry
toluene, KF/Al2O3 (4.5–6 g, 40% by weight) N-tbutyloxycarbonyl-4-piperidone
or cyclohexanone (6 mmol) was added. Then, chloroform (8 mmol) was added
drop wise over a period of 45 min at room temperature. The resulting reaction
mixture was stirred at the same temperature under nitrogen atmosphere for
10–16 h. The reaction mixture was diluted with water (5 mL) and filtered
through
a celite bed. The residue was washed thoroughly with water
(3 Â 5 mL). The combined filtrate was separated and the aqueous layer was
washed with diethyl ether (2 Â 10 mL). The aqueous layer was acidified to ꢀpH
3 with aqueous HCl (3 N) and extracted with ethyl acetate (3 Â 10 mL). The
combined ethyl acetate extract was washed with brine (15 mL) and dried over
anhydrous Na2SO4. The organic layer was filtered and evaporated in vacuo to
obtain a solid compound. In some cases the solid compound obtained was
further purified by crystallization or by silica gel (60–120 mesh) column
chromatography using ethyl acetate and hexane eluents.
In summary, KF/Al2O3 was found to be a useful solid support
base for the Bargellini reaction which is an important alternative
to the Strecker reaction.10 The present KF/Al2O3-promoted
Bargellini reaction introduces the use of an alternative base and
provides a simple procedure and good yields under mild reaction
conditions.
12. Spectroscopic data for compound (3a): Off white solid; mp 100–103 °C; 1H NMR
(400 MHz, CDCl3): d = 1.43–2.05 (m, 10H), 5.59 (br, s, 1H), 6.73 (d, 1H,
J = 7.6 Hz), 6.86 (s, 1H), 6.91 (d, 1H, J = 7.6 Hz), 7.13 (t, 1H, J = 8.0 Hz); 13C NMR
(100 MHz, CDCl3): d = 20.95, 24.96, 32.22, 58.55, 112.07, 112.55, 115.08,
130.05, 133.13, 148.01, 176.90; IR (KBr): 3402, 3269, 3069, 2956, 2936, 2920,
2878, 2855, 1706, 1595, 1521, 1479, 1466, 1453, 1418, 1366, 1314, 1301, 1270,
1227 cmÀ1. MS (AP+) calcd for C13H16ClNO2 253.09, found m/z 253.9 [M+H]+;
CHN analysis for C13H16ClNO2; Theoretical calcd: C, 61.54; H, 6.36; Cl, 13.97; N,
5.52; O, 12.61; Found: C, 61.73; H, 6.27; N, 5.40. Compound (3b): Light yellow
solid; mp 120–122 °C; 1H NMR (400 MHz, CDCl3): d = 1.30–1.90 (m, 10H), 6.52
(d, 2H, J = 8.4 Hz), 6.75 (br, s, 1H), 7.20 (d, 2H, J = 8.8 Hz); 13C NMR (100 MHz,
CDCl3): d = 21.20, 24.97, 32.07, 61.24, 112.56, 118.50, 132.03, 142.11, 178.96;
IR (KBr): 3434, 2942, 2927, 2857, 1697, 1593, 1499, 1460, 1444, 1321, 1288,
1254, 1167 cmÀ1; CHN analysis for C13H16BrNO2; Theoretical calcd: C, 52.36; H,
5.41; Br, 26.80; N, 4.70; O, 10.73; Found: C, 52.66; H, 5.30; N, 4.55. Compound
(3c): Light yellowish white solid; mp 120–123 °C (uncorrected); 1H NMR
Acknowledgments
M.R.R. thanks the UGC for support under the Special Assistance
Program and SAIF, NEHU for providing analytical supports.
References and notes
1. Bargellini, G. Gazz. Chim. Ital. 1906, 36, 329.
2. (a) Korger, G. Chem. Ber. 1963, 96, 10; (b) Butcher, K. J.; Hurst, J. Tetrahedron
Lett. 2009, 50, 2497.

M. R. Rohman, B. Myrboh / Tetrahedron Letters 51 (2010) 4772–4775
4775
(400 MHz, CDCl3): d = 1.14–1.82 (m, 10H), 2.30 (s, 3H), 6.66 (d, 1H, J = 6.8 Hz),
7.02 (t, 1H, J = 7.6 Hz), 7.10 (s, 1H) 7.16 (d, 1H, J = 7.6 Hz); 13C NMR (100 MHz,
CDCl3): d = 22.10, 25.91, 27.53, 33.08, 61.91, 116.99, 121.06, 121.77, 130.29,
138.84, 144.61, 179.84, 199.48; IR (KBr): 3548, 3476, 3415, 3249, 2999, 2962,
2950, 2933, 2857, 1689, 1601, 1588, 1515, 1484, 1451, 1418, 1360, 1314, 1272,
1223, 1209, 1158, 1140, 887, 810 cmÀ1; MS (AP+) calcd for C15H19NO3 261.14,
found m/z 262.2 [M+H]+; CHN analysis C15H19NO3; Theoretical calcd: C, 68.94;
H, 7.33; N, 5.36; O, 18.37; Found: C, 69.19; H, 7.18; N, 5.25. Compound (3d):
Yellow solid; mp 124–127 °C; 1H NMR (400 MHz, CDCl3): d = 1.30–2.24 (m,
10H), 6.63 (d, 1H, J = 8.8 Hz), 6.71 (t, 1H, J = 7.6 Hz), 7.37 (t, 1H, J = 8 Hz), 8.22
(d, 1H, J = 8.4 Hz), 8.47 (s, 1H); 13C NMR (100 MHz, CDCl3): d = 20.99, 24.99,
32.55, 59.78, 115.48, 116.35, 127.34, 133.11, 135.71, 142.95, 180.43; IR (KBr):
3551, 3476, 3414, 3391, 3235, 2942, 2864, 2650, 1707, 1615, 1576, 1504, 1444,
N, 8.13. Compound (3k): Off white solid; mp 135–137 °C; 1H NMR (400 MHz,
CD3OD): d = 1.40–2.02 (m, 10H), 6.73 (t, 1H, J = 6.4 Hz), 6.87 (d, 1H, J = 8.8 Hz),
7.64–7.68 (m, 1H), 7.92 (d, 1H, J = 5.2 Hz); 13C NMR (100 MHz, CD3OD):
d = 22.81, 26.59, 33.88, 62.72, 113.80, 113.84, 141.35, 141.51, 156.67, 179.21;
IR (KBr): 3237, 3154, 3122, 3089, 2945, 2922, 2858, 2848, 1672, 1634, 1609,
1541, 1460, 1446, 1384, 1337, 1297, 1272, 1252 cmÀ1; MS (AP+) calcd for
C
12H16N2O2 220.12, found m/z 221.9 [M+H]+; CHN analysis for C12H16N2O2;
Theoretical calcd: C, 65.43; H, 7.32; N, 12.72; O, 14.53; Found: C, 65.63; H,
7.17; N, 12.85. Compound (3l): Off white solid; mp 120–122 °C; 1H NMR
(400 MHz, CD3OD): d = 1.36 (s, 9H), 2.06–1.94 (m, 4H), 3.20–3.21 (m, 2H),
3.56–3.62 (m, 2H), 6.58 (t, 1H, J = 6.4 Hz), 6.69 (d, 1H, J = 8.4 Hz), 7.46–7.50 (m,
1H), 7.83 (d, 1H, J = 4.8 Hz); 13C NMR (100 MHz, CD3OD): d = 20.81, 28.69,
33.50, 60.25, 81.21, 113.03, 114.12, 140.45, 143.47, 156.44, 157.32, 175.29,
178.21; IR (KBr): 3413, 3272, 3118, 2980, 2938, 2858, 1702, 1672, 1637, 1614,
1539, 1481, 1412, 1394, 1376, 1283, 1249, 1154 cmÀ1; MS (ES+) calcd for
1423, 1348, 1328, 1300, 1268, 1248, 1196, 1164 cmÀ1
; CHN analysis for
C
13H16N2O4; Theoretical calcd: C, 59.08; H, 6.10; N, 10.60; O, 24.22; Found: C,
59.18; H, 6.01; N, 10.55. Compound (3e) Light brown solid; mp 70–73 °C; 1H
NMR (400 MHz, CDCl3): d = 1.19–2.32 (m, 13 H), 2.39 (s, 3H), 6.39 (d, 1H,
J = 8.0 Hz), 6.83–7.30 (m, 3H); 13C NMR (100 MHz, CDCl3): d = 17.48, 17.71,
20.59, 21.41, 25.28, 31.72, 60.76, 115.26, 124.35, 127.45, 131.33, 131.79,
139.17, 178.84; IR (KBr): 3548, 3416, 3236, 2965, 2924, 2857, 1710, 1637,
1618, 1589, 1560, 1514, 1454, 1389, 1353, 1314, 1287 cmÀ1; MS (ES+) calcd for
C
16H23N3O4 321.17, found m/z 322.2 [M+H]+; CHN analysis for C16H23N3O4:
Theoretical calcd: C, 59.80; H, 7.21; N, 13.08; O, 19.91; Found: C, 60.10; H, 7.11;
N, 13.23. Compound (3m): White solid; mp 84–87 °C (uncorrected); 1H NMR
(400 MHz, CDCl3): d = 1.35–2.20 (m, 10H), 6.90–7.29 (m, 5H); 13C NMR
(100 MHz, CDCl3): d = 20.45, 24.44, 31.56, 79.50, 118.16, 121.68, 128.78,
153.97, 178.39; IR (KBr): 3552, 3477, 3416, 3237, 2929, 2857, 1703, 1638,
1618, 1597, 1495, 1449, 1406, 1292, 1269, 1227, 1146 cmÀ1; CHN analysis for
C
15H21NO2 247.16, found m/z 248.0 [M+H]+; CHN analysis for C15H21NO2;
Theoretical calcd: C, 72.84; H, 8.56; N, 5.66; O, 12.94; Found: C, 72.79; H, 8.65;
N, 5.72. Compound (3f): Yellow sticky solid; 1H NMR (400 MHz, DMSO-d6):
d = 1.43–2.12 (m, 10H), 4.96 (s, 1H), 6.47 (d, 1H, J = 2.4 Hz), 6.68 (d, 1H,
J = 8.8 Hz), 7.33 (d, 1H, J = 8.4 Hz), 12.60 (br, s, 1H); 13C NMR (100 MHz, CDCl3):
d = 20.97, 25.05, 32.03, 62.93, 114.08, 118.52, 118.92, 130.04, 133.20, 141.40,
179.63; IR (CHCl3): 3424, 3018, 2940, 2861, 1709,1709, 1593, 1509, 1451,
1415, 1278, 1215, 1156, 1082 cmÀ1; MS (AP+) calcd for C13H15Cl2NO2 287.05,
found m/z 288.0 [M+H]+; CHN analysis for C13H15Cl2NO2; Theoretical calcd: C,
54.18; H, 5.25; Cl, 24.61; N, 4.86; O, 11.10; Found: C, 54.49; H, 5.06; N, 4.43.
Compound (3g): Yellowish white solid; 118–121 °C; 1H NMR (400 MHz, CDCl3):
d = 1.45 (m, 9H), 2.01–2.18 (m, 4H), 3.42–3.58 (m, 4H), 4.31 (br, s, 1H), 6.71 (m,
1H), 6.83 (s, 1H), 6.89 (d, 1H, J = 7.2 Hz), 7.13 (t, 1H, J = 7.2 Hz); 13C NMR
(100 MHz, DMSO-d6): d = 27.99, 57.12, 78.73, 112.19, 112.75, 115.66, 130.23,
133.23, 147.73, 153.84, 176.01; IR (KBr): 3551, 3475, 3415, 3347, 2978, 2927,
2871, 2855, 1699, 1662, 1638, 1618, 1596, 1485, 1408, 1368, 1328, 1291, 1253,
1174, 1159 cmÀ1; CHN analysis for C17H23ClN2O4; Theoretical calcd: C, 57.54;
H, 6.53; Cl, 9.99; N, 7.89; O, 18.04; Found: C, 57.73; H, 6.46; N, 6.02. Compound
(3h): See Ref. 2b. Compound (3i): White solid; mp 110–113 °C; 1H NMR
(400 MHz, CDCl3): d = 1.45 (s, 9H), 1.97–1.99 (m, 2H), 2.12–2.14 (m, 2H), 2.53
(s, 3H), 3.26 (t, 2H, J = 10.4 Hz), 3.73–3.75 (m, 2H), 5.98 (br, s, 1H), 6.82 (d, 1H,
J = 6.8 Hz), 7.21–7.35 (m, 3H); 13C NMR (100 MHz, CDCl3): d = 26.82, 28.58,
32.56, 46.52, 58.59, 80.43, 115.13, 119.67, 120.32, 129.61, 138.18, 145.16,
155.10, 178.05, 199.04; IR (KBr): 3552, 3478, 3414, 3356, 3237, 2982, 2929,
1686, 1677, 1639, 1617, 1603, 1591, 1479, 1453, 1417, 1367, 1325, 1281, 1247,
1161 cmÀ1; CHN analysis for C19H26N2O5; Theoretical calcd: C, 62.97; H, 7.23;
N, 7.73; O, 22.07; Found: C, 63.37; H, 7.00; N, 7.69. Compound (3j): Off white
solid; mp 120–123 °C; 1H NMR (400 MHz, CDCl3): d = 1.45 (s, 9H), 1.99–2.17
(m, 4H), 2.19 (s, 3H), 2.22 (s, 3H), 3.17 (t, 2H, J = 8.0 Hz), 3.79 (m, 2H), 6.23 (br,
s, 1H), 6.43 (d, 1H, J = 8.0 Hz), 6.85 (d, 1H, J = 7.6 Hz), 6.92 (s, 1H); 13C NMR
(100 MHz, CDCl3): d = 17.87, 20.54, 28.58, 32.36, 39.71, 58.38, 80.28, 114.31,
124.90, 127.29, 128.81, 131.81, 139.48, 154.97, 179.34; IR (KBr): 3552, 3480,
3415, 3363, 3236, 2978, 2930, 2870, 1702, 1677, 1638, 1619, 1521, 1454, 1408,
C13H16O3: Theoretical calcd: C, 70.89; H, 7.32; O, 21.79; Found: C, 70.47; H,
7.39. Compound (3n): White solid; mp 54–57 °C; 1H NMR (400 MHz, CDCl3):
d = 1.55–2.00 (m, 10H), 6.97 (t, 1H, J = 8.0 Hz), 7.28 (d, 2H, J = 8.0 Hz); 13C NMR
(100 MHz, CDCl3): d = 21.42, 25.38, 26.83, 27.09, 78.98, 125.09, 129.09, 129.83,
180.10; IR (KBr): 3552, 3473, 3413, 3072, 2938, 2876, 2667, 1709, 1638, 1617,
1564, 1469, 1446, 1407, 1381, 1287, 1273, 1248, 1216, 1192, 1160,1084, 1060,
1043, 1004 cmÀ1; MS (ES+) calcd for C13H14Cl2O3 288.03, found m/z 288.4
[M+H]+; CHN analysis for C13H14Cl2O3: Theoretical calcd: C, 54.00; H, 4.88; Cl,
24.52; O, 16.60; Found: C, 54.30; H, 4.97. Compound (3o): White crystalline
solid; mp 50–53 °C; 1H NMR (400 MHz, CDCl3): d = 1.35–2.11 (m, 10H), 7.30–
7.52 (m, 5H), 9.20 (br, s, 1H); 13C NMR (100 MHz, CDCl3): d = 23.50, 25.22,
33.83, 55.34, 128.67, 129.54, 130.13, 136.98, 179.06; IR (KBr): 3414, 3070,
2968, 2937, 2855, 1694, 1639, 1473, 1451, 1438, 1406, 1306, 1286, 1264, 1253,
1242 cmÀ1; MS (ES+) calcd for C13H16O2S 236.09, found m/z 236.8 [M+H]+;
CHN analysis for C13H16O2S: Theoretical calcd: C, 66.07; H, 6.82; O, 13.54; S,
13.57; Found: C, 66.37; H, 6.69. Compound (3p) White solid; mp 109–112 °C;
1H NMR (400 MHz, CDCl3): d = 1.35–2.10 (m, 10H), 7.29 (d, 2H, J = 8.4 Hz), 7.43
(d, 2H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3): d = 23.48, 25.15, 33.80, 55.48,
128.66, 128.95, 136.13, 138.14, 178.40; IR (KBr): 3552, 3477, 3414, 3230, 2960,
2935, 2857, 1724, 1688, 1638, 1617, 1574, 1474, 1448, 1387, 1285, 1279, 1216,
1183, 1152, 1130, 1090, 1013, 815 cmÀ1; MS (ES+) calcd for C13H15ClO2S
270.05, found m/z 271.2 [M+H]+; CHN analysis for C13H15ClO2S: Theoretical
calcd: C, 57.66; H, 5.58; Cl, 13.09; O, 11.82; S, 11.84; Found: C, 57.86; H, 5.47.
Compound (3q): White solid; mp 148–151 °C (uncorrected); 1H NMR
(400 MHz, CDCl3): d = 1.46 (s, 9H), 1.74–1.80 (m, 2H), 2.05–2.09 (m, 2H),
3.14–3.20 (m, 2H), 3.79–3.82 (m, 2H), 7.31 (d, 2H, J = 8.4 Hz), 7.42 (d, 2H,
J = 8.4 Hz); 13C NMR (100 MHz, CDCl3): d = 28.40, 32.69, 53.58, 80.12, 127.76,
129.19, 136.54, 138.16, 154.71, 176.78; IR (KBr): 3547, 3416, 3006, 2972, 2921,
2865, 2750, 2661, 1714, 1631, 1477, 1462, 1444, 1390, 1368, 1344, 1293, 1265,
1226, 1166, 1092, 1023, 1014, 823 cmÀ1; MS (ES+) calcd for C17H22ClNO4S
371.10, found m/z 372.3 [M+H]+; CHN analysis for C17H22ClNO4S: Theoretical
calcd: C, 54.91; H, 5.96; Cl, 9.53; N, 3.77; O, 17.21; S, 8.62; Found: C, 55.45; H,
6.10; N, 3.64.
1367, 1316, 1282, 1248, 1160, 1131 cmÀ1
Theoretical calcd: C, 65.49; H, 8.10; N, 8.04; O, 18.37; Found: C, 65.29; H, 8.05;
; CHN analysis for C19H28N2O4;