Montmorillonite K10 clay: An efficient catalyst for the one-pot stereoselective synthesis of β-acetamido ketones

Article abstract of DOI:10.1021/jo020734p

An efficient one-pot three-component coupling process for the synthesis of β-acetamido ketones catalyzed by montmorillonite K10 clay is described. The reaction is highly stereoselective and the catalyst can be recycled.

Full text of DOI:10.1021/jo020734p

Mon tm or illon ite K10 Cla y: An Efficien t
Ca ta lyst for th e On e-P ot Ster eoselective
Syn th esis of â-Aceta m id o Keton es
SCHEME 1
†
‡
,†,‡
D. Bahulayan, Saibal Kumar Das, and J aved Iqbal*
Regional Research Laboratory (CSIR),
Trivandrum-695 019, Kerala, India, and Dr. Reddy’s
Laboratories Ltd., Discovery Research, Discovery Chemistry,
Miyapur, Hyderabad 500 050, India
mination of alkyl benzenes,3 oxidation of organic sulfides
e
to sulfoxides,3f the synthesis of biomarkers, oxidative
3g
3h
demethylation of methylphenols to benzoquinones, (2,5)
intramolecular ene cyclization,3 Michael addition, Boc
i
3j
javediqbaldrf@hotmail.com
Received December 10, 2002
3k
group removal from aromatic amines, the Diels-Alder
reaction,3 and so on. Mont. K10 has also been used in
many microwave reactions under liquid phase as well as
in solvent-free conditions.4
l
Abstr a ct: An efficient one-pot three-component coupling
process for the synthesis of â-acetamido ketones catalyzed
by montmorillonite K10 clay is described. The reaction is
highly stereoselective and the catalyst can be recycled.
5
The multicomponent coupling reactions are emerging
as useful tools for synthesizing small drug-like molecules
with several degrees of structural diversity. Pioneering
work by several research groups in this area has already
established the versatility and uniqueness of one-pot
multicomponent coupling protocols as a powerful meth-
odology for the synthesis of diverse structural scaffolds
required in the search of novel therapeutic molecules. In
earlier studies6 we have demonstrated that cobalt(II)
chloride catalyzes the coupling between a ketone or
ketoester, an aldehyde, and acetonitrile in the presence
of acetyl chloride to provide a general route to â-aceta-
mido carbonyl compounds. Encouraged by these results,
we have now explored the possibilities of Mont. K10-
catalyzed three-component one-pot stereoselective syn-
thesis of â-acetamido ketone 1 following the protocol
described by us earlier (Scheme 1).
As described in our earlier work,6f an aldehyde and a
ketone in equimolar ratios were stirred for 7 h at 70 °C
in acetonitrile (25 mL) with acetyl chloride (4 equiv) in
the presence of 2 g of K10 clay to afford the acetamido
ketones 1 in good to excellent yields. As shown in Table
Clays are known for their Lewis acid activity and have
acquired an important place in synthetic organic chem-
istry. Clays have been widely used in organic chemistry
1
over two decades. Their importance is likely to increase
with demanding environmental legislation, public and
corporate pressure, and the drive toward clean technol-
ogy. The use of efficient solid catalysts can go a long way
2
toward achieving these goals. While many reagents are
used in stoichiometric amounts the development of
catalytic use is genuinely a valuable addition to organic
reactions especially in the liquid phase. It is important
to assess the potential of these solid acids. These sup-
ported reagents, especially Montmorillonite K10 (Mont.
K10), are most widely studied and found useful in many
3
a
reactions, viz., the synthesis of γ-lactones, the synthesis
of fused heterocycles,3b the Friedel-Crafts reaction,
3c
3
d
acetal and ketal deprotection reactions, selective bro-
1
, we studied the reaction of acetophenone with various
†
Regional Research Laboratory (CSIR).
Dr. Reddy’s Laboratories Ltd.
substituted benzaldehydes (Table 1, entries 2-8). The
reactions of ortho-substituted benzaldehydes (entries
2-4) afforded higher yields of the desired â-acetamido
ketones 1b-d and maximum yield (88%) was obtained
with o-nitrobenzaldehyde (Table 1, entry 4). Interestingly
the reaction between salicylaldehyde and acetophonone
‡
(1) (a) Clark, J . H. Catalysis of Organic Reactions by Supported
Inorganic Reagents; VCH: New York, 1994. (b) Corn e´ lis, A.; Laszlo,
P. Synlett 1994, 155. (c) Clark, J . H.; Macquarrie, D. J . Chem. Commun.
998, 853. (d) Varma, R. S.; Naicker, K. P.; Aschberger, J . Synth.
Commun. 1999, 29, 2823. (e) Meshram, H. M.; Sumithra, G.; Reddy,
G. S.; Ganesh, Y. S. S.; Yadav, J . S. Synth. Commun. 1999, 29, 2807.
f) Bahulayan, D.; Sukumar, R.; Sabu, K. R.; Lalithambika, M. Green
1
(
Chem. 1999, 1, 191. (g) Choudary, B. M.; Sateesh, M.; Kantham, M.
L.; Rao, K. K.; Ramprasad, K. V.; Raghavan, K. V.; Sharma, J . A. R.
P. Chem. Commun. 2000, 25, 1. (h) Samajdar, S.; Becker, F. R.; Naik,
P. K. Tetrahedron Lett. 2000, 41, 8017. (i) Bahulayan, D.; Narayan,
G.; Sreekumar, V.; Lalithambika, M. Synth. Commun. 2002, 32, 3565.
(4) (a) Texier-Boullet, F.; Latouche, R.; Hamelin, J . Tetrahedron Lett.
1993, 34, 2123. (b) Perez, E. R.; Marrero, A. L.; Perez, R.; Autie, M. A.
Tetrahedron Lett. 1995, 36, 1779. (c) Ben-Alloum, A.; Bakkas, S.;
Soufiaoui, M. Tetrahedron Lett. 1997, 38, 6395. (d) Bolourtchian, M.;
Zadmard, R.; Saidi, M. R. Synth. Commun. 1998, 28, 2017. (e)
Mojtahedi, M. M.; Saidi, M. R.; Bolourtchian, M. J . Chem. Res. Synop.
1999, 128. (f) Bougrin, K.; Loupy, A.; Petit, A.; Daou, B.; Soufiaoui, M.
Tetrahedron 2001, 57, 163.
(5) (a) For a review see: Domling, A.; Ugi, I. Angew. Chem., Int.
Ed. 2000, 39, 3168. (b) Terret, N. K.; Gardner, M.; Gordon, D. W.;
Kobylecki, R. J .; Steele, J . Tetrahedron 1995, 51, 8135. (c) Thomson,
L. A.; Ellman, J . A. Chem. Rev. 1996, 96, 555. (d) Ellman, J . A. Acc.
Chem. Res. 1996, 29, 132.
(6) (a) Bhatia, B.; Reddy, M. M.; Iqbal, J . J . Chem. Soc., Chem.
Commun. 1994, 713. (b) Reddy, M. M.; Bhatia, B.; Iqbal, J . Tetrahedron
Lett. 1995, 36, 4877. (c) Mukhopadhyay, M.; Bhatia, B.; Iqbal, J .
Tetrahedron Lett. 1997, 38, 1083. (d) Prbhakaran, E. N.; Iqbal, J . J .
Org. Chem. 1999, 64, 3339. (e) For related three-component coupling,
see: Armstrong, R. W.; Combs, A. W.; Templest, P. A.; Brown, S. D.;
Keating, T. A. Acc. Chem. Res. 1996, 29, 123. (f) Rao, I. N.; Prabhaka-
ran, E. N.; Das, S. K.; Iqbal, J . J . Org. Chem. 2003, 68, 4079.
(
(
2) Clark, J . H.; Macquarrie, D. J . Chem. Soc. Rev. 1996, 303.
3) (a) Roudier, J .-F.; Foucaud, A. Tetrahedron Lett. 1984, 25, 4375.
(b) Chunchatprasert, L.; Rao, K. R. N.; Shannon, P. V. R. J . Chem.
Soc., Perkin. Trans. 1 1992, 1779. (c) Sieskind, O.; Albrecht, P.
Tetrahedron Lett. 1993, 34, 1197. (d) Gautier, E. C. L.; Graham, A. E.;
McKillop, A.; Standen, S. P.; Taylor, R. L. K. Tetrahedron Lett. 1997,
3
5
8, 1881. (e) Venkatachalapathy, C.; Pitchumani, K. Tetrahedron 1997,
3, 2581. (f) Kannan, P.; Sevvel, R.; Rajagopal, S.; Pitchumani, K.;
Srinivasan, C. Tetrahedron 1997, 53, 7635. (g) Li, T.-S.; Wang, J .-X.;
Zheng, X.-J . J . Chem. Soc., Perkin. Trans. 1 1998, 3957. (h) Bushmelev,
V. A.; Genaev, A. M.; Shubin, V. G. Russ. J . Org. Chem. 1999, 35, 62.
(
(
i) Ohmura, H.; Smyth, G. D.; Mikami, K. J . Org. Chem. 1999, 64, 6056.
j) Poupaert, J . H.; Bukuru, J .; Gozzo, A. Monatsh. Chem. 1999, 130,
9
29. (k) Shaikh, N. S.; Gajare, A. S.; Deshpande, V. H.; Bedekar, A. V.
Tetrahedron Lett. 2000, 41, 385. (l) Avalos, M.; Babiano, R.; Bravo, J .
L.; Cintas, P.; J imenez, J . L.; Palacios, J . C. Tetrahedron Lett. 1998,
3
9, 9301.
1
0.1021/jo020734p CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/06/2003
J . Org. Chem. 2003, 68, 5735-5738
5735

TABLE 1. Mon tm or illon ite K10-Ca ta lyzed F or m a tion of
â-Aceta m id o Keton es
TABLE 2. Mon tm or illon ite K10-Ca ta lyzed F or m a tion of
â-Aceta m id o Keton es fr om r-Su bsitu ted Keton es
*
Yield of the isolated anti-diastereomers (stereochemistry
assigned based on the coupling constant of methine protones).
a
The yield is based on the weight of the pure products obtained
a
Reactions at 70 °C. b Reaction at rt. c Syn/anti ratio determined
from aqueous workup.
from 1H NMR of the crude mixture.
yielded the corresponding â-acetamido ketone 1c (Table
p-methylbenzaldehyde and in both cases the anti-
diastereomers 2a and 2b, respectively, were obtained as
major products (Table 2, entries 1 and 2). The separation
of the products was done by chromatography on silica
gel column. In a similar manner propiophenone also
yielded the corresponding anti-diastereomers 2c-e (Table
2, entries 3-5) and again salicylaldehyde afforded a
product without acetylating the OH group (Table 2, entry
4). Interestingly, the reactions with cyclohexanone were
found to proceed smoothly at room temperature to afford
2f-h (Table 2, entries 6-8). When these reactions were
conducted at 70 °C, polymeric materials were isolated as
end products.
We have also examined the reusability of the catalyst
as the latter obtained after the removal of the product
was repeatedly washed with acetonitrile and finally with
acetone. The acetone-washed catalyst was dried in an air
oven at 110 °C for 3 h and used for the reactions. We
have not carried out reactions with the several batches
of recovered catalyst; however, repetition with one batch
indicated that its efficiency is similar to that of the fresh
catalyst. The performance of the recovered catalyst
during the synthesis of â-acetamido ketones was found
to be satisfactory and no considerable variation in yield,
1
, entry 3) and not the OH-acetylated product, which is
in contrast to the observation made in the corresponding
6
f
cobalt-catalyzed reactions. We do not have any definite
explanation for this anomaly but it appears that cobalt
is also an efficient catalyst for the acylation of phenolic
groups. The reactions of 4-nitro, 4-cyano, 3-nitro, and
4
-carboxy benzaldehydes with acetophenone yielded the
corresponding â-acetamido ketones in 64-75% yields
Table 1, entries 5-8). The isolation of these products
(
was pretty much straightforward as the catalyst was
removed by filtration and the filtrate was poured into
ice-cold water, which resulted in precipitation of the
desired â-acetamido ketones. The precipitated solid ma-
terials were filtered, dried, and washed with diethyl ether
1
to afford highly pure â-acetamido ketones (by H NMR).
In our previous publication,6d we have shown that
aromatic aldehydes reacted with R-substituted ketones
to afford the â-acetamido ketones 2 in a diastereoselective
manner. To demonstrate the versatility of this catalyst
(K10 clay) we have examined the reactions of benzalde-
hyde derivatives with ethyl methyl ketone, propiophe-
none, and cyclohexanone. With ethyl methyl ketone,
we have studied the reactions of benzaldehyde and
5
736 J . Org. Chem., Vol. 68, No. 14, 2003

1367, 1202, 758, 685 cm-1; MS m/z 304 (M + 2), 207, 182, 148,
stereoselectivity, and efficiency was noticed from the
initial observations.
In conclusion, we have demonstrated an alternative
simple procedure for the stereoselective synthesis of
â-acetamido ketones using an eco-friendly, reusable, and
inexpensive catalyst.
1
20, 105, 69, 55.
â-Aceta m id o-â-(4-n itr op h en yl)p r op iop h en on e (1e). Mp
1
1
2
48-149 °C; H NMR (300 MHz, CDCl
3
) δ 8.16 (d, J ) 8.4 Hz,
H), 7.89 (d, J ) 9.6 Hz, 2H), 7.62-7.46 (m, 5H), 7.02 (d, J )
9.0 Hz, 1H), 5.66 (s, 1H), 3.80 (dd, J ) 4.8 and 17.6 Hz, 1H),
3.50 (dd, J ) 5.2 and 17.6 Hz, 1H), 2.0 (s, 3H); FT-IR (KBr) νmax
-1
3
310, 1686, 1645, 1580, 1513, 1352, 1300, 751 cm ; MS m/z 311
(
5
M - 1), 295, 270, 194, 175, 165, 151, 129, 120, 105, 102, 90, 68,
Exp er im en ta l Section
4.
â-Aceta m id o-â-(4-cya n op h en yl)p r op iop h en on e (1f). Mp
8-90 °C; 1H NMR (300 MHz, CDCl
) δ 7.91 (d, J ) 8.1 Hz,
H), 7.80 (s, 1H), 7.61-7.59 (m, 3H), 7.49-7.41 (m, 4H), 5.57
A Typ ica l P r oced u r e for th e Syn th esis of â-Aceta m id o
Keton e 1a . To a stirred suspension of Mont. K10 (2 g) in
acetonitrile (25 mL) were added benzaldehyde (1.06 g, 10 mmol),
acetophenone (1.20 g, 10 mmol), and acetyl chloride (4.0 mL)
and the mixture was allowed to stand at the same temperature
for 15 min. The temperature was increased to 70 °C and the
stirring was continued for 7 h. The reaction mixture was filtered
to remove the catalyst and the filtrate was poured into ice-cold
water and stirred for 1 h. The precipitated solid was filtered
and dried. The dried sample was washed with diethyl ether (3
8
2
(
3
d, J ) 6.7 Hz, 1H), 3.70 (dd, J ) 6.4 and 17.3 Hz, 1H), 3.43 (dd,
J ) 5.9 and 16.6 Hz, 1H), 1.99 (s, 3H); FT-IR (KBr) νmax 3297,
2
MS m/z 292 (M + 1), 231, 145, 129, 120, 91, 79.
-1
236, 1699, 1646, 1533, 1447, 1228, 983, 758, 685, 552 cm
;
â-Aceta m id o-â-(3-n itr op h en yl)p r op iop h en on e (1g). Mp
1
1
8
5
1
1
12-115 °C; H NMR (300 MHz, CDCl ) δ 8.39-8.31 (m, 1H),
3
.06 (d, J ) 6.4 Hz, 2H), 7.94 (d, J ) 6.0 Hz, 2H), 7.48 (d, J )
.9 Hz, 2H), 5.62 (s, 1H), 3.72 (d, J ) 12.3 Hz, 1H), 3.44 (d, J )
6.6 Hz, 1H), 1.95 (s, 3H); FT-IR (KBr) νmax 3277, 1686, 1639,
×
15 mL) and again dried. The â-acetamido ketone 1a (80%,
mp 102-104 °C) thus obtained was sufficiently pure as indicated
-
1
527, 1341, 1288, 1228, 751, 685, 632 cm ; MS m/z 267 (M + 1
NO ), 212, 196, 147, 120, 89, 71, 40.
â-Acet a m id o-â-(4-ca r b oxyp h en yl)p r op iop h en on e (1h ).
1
by H NMR. The same procedure was repeated for all acetophe-
-
2
none and propiophenone reactions.
The products obtained from the reactions of ethyl methyl
ketone and cyclohexanone were separated by silica gel chroma-
tography. In these cases the workup procedure is little different
from the earlier case. After removal of the catalyst the reaction
mixture was concentrated to remove the acetonitrile and the
residue was dissolved in chloroform (20 mL). The chloroform
solution was washed with 2% NaOH solution (2 × 20 mL) and
1
Mp 228-230 °C; H NMR (300 MHz, DMSO) δ 10.09 (s, 1H),
8
1
1
.42 (s, 1H), 8.11-7.86 (m, 5H), 7.61-7.49 (m, 4H), 5.39 (s, 1H),
.88 (s, 3H); FT-IR (KBr) νmax 3051-2826, 1719, 1686, 1580,
-1
500, 1420, 1295, 1248, 1195, 1102, 758, 685 cm ; MS m/z 311
+
(M ), 266, 219, 211, 146, 120, 81, 60, 52.
N-1-[(1S,2R)-2-Met h yl-3-oxo-1-p h en ylb u t yl]a cet a m id e
1
(
2a ). Mp 126-127 °C; H NMR (300 MHz, CDCl
3
) δ 7.33-7.21
2 4
the organic layer was washed with brine, dried over Na SO ,
(m, 5H), 7.12 (d, J ) 7.8 Hz, 1H), 5.16 (dd, J ) 5.9 and 9.0 Hz,
and concentrated. The residue was purified on a column of silica
gel with petroleum ether-chloroform (1:1) for ethyl methyl
ketone reactions and ethyl acetate-petroleum ether (1:1) for
cyclohexanone reactions to afford the corresponding â-acetamido
ketones as solids. The solids were crystallized from diethyl
ether-petroleum ether.
1
6
1
H), 3.10 (dd, J ) 6.9 and 14.2 Hz, 1H), 2.04 (d, J ) 10.2 Hz,
13
H), 1.17 (d, J ) 7.1 Hz, 3H); C NMR (75 MHz, CDCl
3
) δ 213.4,
69.7, 140.5, 128.5, 127.3, 126.25, 55.2, 51.1, 29.65, 23.23, 15.13;
FT-IR (KBr) νmax 3290, 1719, 1653, 1553, 1374, 1308, 1129, 758,
7
7
-1
+
04 cm ; MS m/z 219 (M ), 176, 148, 134, 118, 106, 104, 91,
7, 58, 43.
â-Aceta m id o-â-p h en ylp r op iop h en on e (1a ). Mp 102-104
N-1-[(1S,2R)-2-Met h yl-1-(4-m et h ylp h en yl)-3-oxob u t yl]-
1
°
C; H NMR (300 MHz, CDCl
3
) δ 7.90 (d, J ) 7.3 Hz, 2H), 7.58-
1
3
a ceta m id e (2b). Mp 133-134 °C; H NMR (300 MHz, CDCl )
7
1
6
1
4
1
1
.20 (m, 8H), 6.77 (d, J ) 8.9 Hz, 1H), 5.56 (dd, J ) 5.7 and
3.4 Hz, 1H), 3.77 (dd, J ) 5.2 and 16.9 Hz, 1H), 3.43 (dd, J )
.1 and 16.9 Hz, 1H), 2.0 (s, 3H); 13C NMR (75 MHz, CDCl
δ 7.1 (s, 4H), 6.93 (d, J ) 8.4 Hz, 1H), 5.12 (dd, J ) 5.8 and 9.0
Hz, 1H), 3.07 (dd, J ) 6.6 and 13.2 Hz, 1H), 2.3 (s, 3H), 2.17-
3
) δ
1
1
5
1
13
3
.97 (m, 6H), 1.19-1.08 (m, 3H); C NMR (75 MHz, CDCl ) δ
98.5, 169.45, 140.8, 133.46, 128.6, 128.07, 127.3, 126.4, 49.8,
83.85, 169.53, 137.74, 137.01, 129.28, 126.87, 126.24, 55.16,
3.14, 23.37; FT-IR (KBr) νmax 3423, 1772, 1659, 1500, 1374,
1.28, 29.62, 23.28, 20.92, 15.11; FT-IR (KBr) νmax 3297, 2985,
-
1
295, 1188, 1023, 704, 585 cm ; MS m/z 266 (M - 1), 208, 179,
-1
706, 1653, 1553, 1451, 1427, 1374, 1308, 1135, 724, 545 cm
;
62, 120, 107, 106, 77, 50.
+
MS m/z 233 (M ), 190, 174, 163, 148, 131, 121, 106, 90, 88, 76,
62, 51.
â-Aceta m id o-â-(2-n itr op h en yl)p r op iop h en on e (1b). Mp
1
1
)
7
86-188 °C; H NMR (300 MHz, CDCl
3
+ DMSO) δ 8.29 (d, J
N-1-[(1S,2R)-2-Met h yl-3-oxo-1,3-d ip h en ylp r op yl]a cet a -
6.6 Hz, 1H), 7.97 (d, J ) 7.3 Hz, 2H), 7.88 (d, J ) 8.1 Hz, 1H),
1
m id e (2c). Mp 140 °C; H NMR (300 MHz, DMSO) δ 8.44 (d, J
)
5
.72 (d, J ) 7.2 Hz, 1H), 7.65-7.51 (m, 2H), 7.51-7.40 (m, 3H),
.90 (dd, J ) 3.9 and 15.8 Hz, 1H), 3.65 (dd, J ) 9.2 and 17.3
7 Hz, 1H), 8.16 (s, 1H), 7.77-7.53 (m, 4H), 7.43-7.30 (m, 5H),
5
.09 (s, 1H), 1.83 (s, 1H), 1.65 (s, 3H), 0.80 (s, 3H); FT-IR (KBr)
max 3290, 2972, 1679, 1653, 1546, 1454, 1367.9, 970, 704, 605
1
3
Hz, 1H), 3.48 (dd, J ) 3.8 and 17.3 Hz, 1H), 1.25 (s, 3H);
C
ν
NMR (75 MHz, CDCl
35.4, 132.5, 132.49, 127.8, 127.7, 127.1, 127.05, 123.35, 44.83,
3
+ DMSO) δ 195.38, 168.93, 147.34, 137.3,
-1
+
cm ; MS m/z 281 (M ), 238, 221, 207, 176, 165, 148, 132, 118,
1
4
1
3
1
1
05.
2.89, 21.76; FT-IR (KBr) νmax 3310, 3071, 1686, 1646, 1580,
N-1-[(1S,2R)-1-(2-Hyd r oxyp h en yl)-2-m eth yl-3-oxo-3-p h e-
-
1
+
513, 1354, 1301, 1222, 990, 751, 685 cm ; MS m/z 312 (M ),
11 (M - 1), 267, 235, 211, 202, 194, 165, 153, 146, 134, 123,
20, 105, 85, 71, 40.
n ylp r op yl]a ceta m id e (2d ). Mp 142 °C; 1H NMR (300 MHz,
DMSO) δ 8.09-8.03 (m, 2H), 7.97-7.83 (m, 3H), 7.62-7.03 (m,
4
1H), 1.9 (s, 3H), 1.68 (s, 3H); FT-IR (KBr) νmax 3390, 1759, 1679,
1646, 1520, 1487, 1447, 1367, 1195, 758, 585 cm ; MS m/z 297
(M ), 251, 237, 221, 199, 189, 174, 156, 148, 121, 105.
H), 6.81 (d, J ) 8.8 Hz, 1H), 5.57 (d, J ) 9.6 Hz, 1H), 4.07 (m,
â-Acet a m id o-â-(2-h yd r oxyp h en yl)p r op iop h en on e (1c).
1
-1
Mp 129-130 °C; H NMR (300 MHz, CDCl
3
) δ 8.17 (d, J ) 5.6
+
Hz, 2H), 7.89 (d, J ) 6.0 Hz, 2H), 7.60-7.47 (m, 5H), 6.99 (s,
1
1
1
4
1
H), 5.67 (s, 1H), 3.79 (d, J ) 7.4 Hz, 1H), 3.53 (d, J ) 7.2 Hz,
N-1-[(1S,2R)-2-Meth yl-1-(2-n itr op h en yl)-3-oxo-3-p h en yl-
H), 2.08 (s, 3H); 13C NMR (75 MHz, CDCl
) δ 198.16, 178.46,
1
3
p r op yl]a ceta m id e (2e). Mp 122-124 °C; H NMR (300 MHz,
36.09, 134.02, 130.94, 128.85, 128.06, 127.80, 123.80, 121.65,
9.14, 42.53, 37.08; FT-IR (KBr) νmax 3290, 1686, 1646, 1600,
507, 1454, 1348, 1295, 857, 751, 685, 592 cm-1; MS m/z 281
DMSO) δ 8.52-8.44 (m, 1H), 8.14-7.97 (m, 1H), 7.80-7.30 (m,
8H), 5.67 (dd, J ) 7.7 and 13.7 Hz, 1H), 4.13-3.98 (m, 1H), 1.56
(s, 3H), 0.87 (d, J ) 7.0 Hz, 3H); FT-IR (KBr) ν
max
-
3264, 3058,
1
(M - 2), 237, 208, 207, 194, 175, 165, 152, 121, 102, 89, 76.
1979, 1646, 1527, 1454, 1354, 1295, 970, 711 cm ; MS m/z 327
(M + 1), 280, 266, 237, 211, 193, 177, 133, 120, 105.
â-Aceta m id o-â-(2-ch lor op h en yl)p r op iop h en on e (1d ). Mp
1
1
2
5
3
35-136 °C; H NMR (300 MHz, CDCl
3
) δ 7.89 (d, J ) 7.4 Hz,
N -1-{(1S )-1-[(2R )-2-Oxocycloh e xyl]-1-p h e n ylm e t h yl}-
1
H), 7.57-7.13 (m, 6H), 7.0 (s, 1H), 5.83 (s, 1H), 3.74 (dd, J )
.5 and 16.4 Hz, 1H), 3.46 (dd, J ) 5.1 and 16.6 Hz, 1H), 2.0 (s,
H); FT-IR (KBr) νmax 3290, 3065, 2362, 1688, 1646, 1546.9,
a ceta m id e (2f). Mp 221-222 °C; H NMR (300 MHz, CDCl
8.52 (d, J ) 8.4 Hz, 1H), 7.30-7.10 (m, 5H), 6.26 (s, 1H), 5.77
(d, J ) 8.3 Hz, 1H), 2.7 (br s, 1H), 2.58 (d, J ) 5.6 Hz, 2H), 2.44
3
) δ
J . Org. Chem, Vol. 68, No. 14, 2003 5737

(
3
d, J ) 5.4 Hz, 2H), 2.27 (m, 4H), 2.0 (s, 3H); FT-IR (KBr) νmax
1646, 1600, 1520, 1341, 1228, 850, 698 cm-1; MS m/z 268 (M +
2 - NO ), 241, 232, 214, 190, 176, 150, 140, 116, 103.
-
1
270, 1699, 1646, 1546.9, 1367.9, 1222, 698 cm ; MS m/z 245
2
+
(M ), 226, 201, 149, 104, 91, 76, 63, 43.
Ack n ow led gm en t. D.B. thanks S.E.R.C., Depart-
ment of Science & Technology, Government of India for
financial assistance under the Fast Track Scheme for
young scientists (SR/FTP/CS/17/2000).
N-1-{(1S)-1-(2-Nit r op h en yl)-1-[(2R)-2-oxocycloh exyl]-
1
m eth yl}a ceta m id e (2g). Mp 139-140 °C; H NMR (300 MHz,
CDCl
2
ν
7
1
3
) δ 8.18 (d, J ) 7.3 Hz, 1H), 7.82 (s, 2H), 7.69-7.54 (m,
H), 5.57 (m, 1H), 2.64-2.51 (m, 8H), 1.65 (s, 3H); FT-IR (KBr)
max 3423, 2932, 1666, 1599, 1520, 1341, 1267, 1175, 1142, 970,
Su p p or tin g In for m a tion Ava ila ble: 1H NMR and MS
spectra of 1a ,c,d ,e and 2a ,b,e, f, 13C NMR spectra of 1a ,c,b
and 2b, MS of 1a ,c,d ,e and 2a ,b,e,f, and FT-IR spectra of
-
1
18, 519 cm ; MS m/z 291 (M + 1), 275, 254, 222, 218, 198,
93, 186, 169, 154, 136, 125, 111, 107.
N-1-{(1S)-1-(4-Nit r op h en yl)-1-[(2R)-2-oxocycloh exyl]-
1
a ,c,d and 2a ,b,e,f. This material is available free of charge
1
m eth yl}a ceta m id e (2h ). Mp 192-194 °C; H NMR (300 MHz,
via the Internet at http://pubs.acs.org.
DMSO) δ 8.34-8.24 (m, 2H), 7.75-7.62 (m, 2H), 5.48 (s, 1H),
2
.23-2.20 (m, 8H), 1.81 (s, 3H); FT-IR (KBr) νmax 3383, 2933,
J O020734P
5
738 J . Org. Chem., Vol. 68, No. 14, 2003