Iron(III) chloride-catalyzed convenient one-pot synthesis of β-acetamido carbonyl compounds

Article abstract of DOI:10.1016/j.tet.2007.04.019

A one-pot multi-component reaction of aldehydes, enolizable ketones or 1,3-dicarbonyls, acetonitrile/benzonitrile, and acetyl chloride is described for the preparation of β-acetamido carbonyl compounds using FeCl₃·6H₂O as a mild, inexpensive, and highly efficient catalyst. The effect of substrate as well as substituent for multi-component reaction versus Knoevenagel condensation is also illustrated. The key features of this methodology are operational simplicity, mild reaction conditions, and good yields.

Full text of DOI:10.1016/j.tet.2007.04.019

Tetrahedron 63 (2007) 5593–5601
Iron(III) chloride-catalyzed convenient one-pot synthesis
of b-acetamido carbonyl compounds
*
Abu T. Khan, Tasneem Parvin and Lokman H. Choudhury
Indian Institute of Technology Guwahati, Department of Chemistry, Guwahati 781 039, India
Received 2 January 2007; revised 13 March 2007; accepted 5 April 2007
Available online 14 April 2007
Abstract—A one-pot multi-component reaction of aldehydes, enolizable ketones or 1,3-dicarbonyls, acetonitrile/benzonitrile, and acetyl
chloride is described for the preparation of b-acetamido carbonyl compounds using FeCl3$6H2O as a mild, inexpensive, and highly efficient
catalyst. The effect of substrate as well as substituent for multi-component reaction versus Knoevenagel condensation is also illustrated. The
key features of this methodology are operational simplicity, mild reaction conditions, and good yields.
Ó 2007 Published by Elsevier Ltd.
1. Introduction
as for the synthesis of various bioactive molecules such as
antibiotic nikkomycins or neopolyoxines.3 The conventional
way for the preparation of these compounds is the Dankin–
West reaction using a-amino acids and acetic anhydride.4
Later on, Iqbal et al. introduced both CoCl25 and Montmoril-
lonite K-10 clay6 catalyzed multi-component reactions
involving an aldehyde, enolizable ketone or keto ester in
acetonitrile, and acetyl chloride for the one-pot synthesis of
b-acetamido carbonyl compounds. Subsequently, Cu(OTf)2/
Sc(OTf)3,7 silica supported sulfuric acid,8 BiOCl,9
ZrOCl2$8H2O,10 H6P2W18O62,11a H3PW12O40,11b I2,12 and
Amberlyst-1513 are reported as effective catalysts for the
synthesis of b-acetamido carbonyl compounds. Recently,
we have introduced CeCl3$7H2O as an efficient catalyst
for the preparation of b-acetamido carbonyl compounds by
MCRs.14 Though the above methodologies are quite useful,
most of the methods encounter some limitations, such as re-
quirement of expensive catalysts, longer reaction time, and
Multi-component reactions (MCRs) are a promising and
vital field of chemistry because the synthesis of complicated
molecules can be achieved in a very fast, efficient, and time-
saving manner without the isolation of any intermediate. As
a result, it requires minimum effort, which minimizes the
environmental loading and is acceptable from a ‘Green
Chemistry’ point of view. In recent years, the discovery of
novel MCRs has become an increasingly active area of re-
search, yielding novel chemical scaffolds for drug discovery.
Thus, the development of new multi-component reactions is
a popular area of research in current organic chemistry.1
The synthesis of b-acetamido carbonyl compounds has
gained considerable attention in organic synthesis, owing
to their importance as valuable building blocks for the prep-
aration of 1,3-amino alcohols2a,b or b-amino acids,2c as well
O
NHCOR1
R
O
.
FeCl3 6H2O (10 mol %)
RCHO
+
CH3COCl, R1CN, rt
R = benzylic, R1= CH3 / Ph
R1CONH
R1CONH
O
O
CHO
.
O
O
FeCl3 6H2O (10 mol %)
O
+
+
R1CN, CH3COCl, rt
R2
R2
R2
O
X
X
X
syn
anti
Scheme 1.
* Corresponding author. Tel.: +91 361 2582305; fax: +91 361 2582349; e-mail: atk@iitg.ernet.in
0040–4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.04.019

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A. T. Khan et al. / Tetrahedron 63 (2007) 5593–5601
harsh reaction conditions. It is thus evident that there remains
a wide scope for the development of clean and efficient
methodologies for the preparation of b-acetamido carbonyl
compounds using a cheap and readily available catalyst.
2. Results and discussion
For the preliminary study, 4-chlorobenzaldehyde (2 mmol)
andacetophenone(2 mmol)inacetonitrile(5 mL) werestirred
in the presence of a catalytic amount of FeCl3$6H2O
(10 mol %)andacetylchloride(3 mmol) atroomtemperature.
The progress of the reaction was monitored by TLC. After
completionofthereaction,itwaspouredintoabeakercontain-
ing crushed ice to solidify the product. On solidification of the
product, it was filtered off and dried to obtain the correspond-
ing b-acetamido ketone. The solid product was recrystallized
from ethyl acetate and hexane, and fully characterized by re-
FeCl3$6H2O has emerged as a potentially useful Lewis acid
and has been extensively used in various organic transforma-
tions.15 Due to its unique catalytic properties, it has been
used for a plethora of organic transformations such as the
construction of 10H-indeno[1,2-b]triphenylene skeletons
by oxidative cyclization,16 cleavage of silyl protecting
groups,17 amino halogenation of arylmethylenecyclopro-
panes and arylvinylidenecyclopropanes,18 hydroarylation
of styrenes,19 one-pot synthesis of 1,2-dihydro-2-oxo-3-
pyridinecarboxylate derivatives,20 Friedlander synthesis of
quinolines,21 one-pot synthesis of homoallyl benzyl ethers
from aldehydes,22 and synthesis of nicotinic acid deriva-
tives,23 etc (Scheme 1).
1
cording IR, H NMR, and elemental analysis. Encouraged
by this result, a widevariety of aromatic aldehydes, containing
both electron withdrawing and donating substituents, were
treated under the same experimental conditions and afforded
the corresponding b-acetamido ketones (Table 1, entries 2–
9) in good to excellent yields. Similarly, a,b-unsaturated
Table 1. FeCl3$6H2O catalyzed multi-component reaction for the preparation of b-acetamido ketones
O
NHCOR
O
CHO
FeCl3 6H2O (10 mol %)
CH3COCl, RCN, rt
+
X
X
Entry
1
b-Acetamido ketonesa
NHAc
Time (h)
Yieldb,c (%)
Entry
8
b-Acetamido ketonesa
NHAc
Time (h)
10
Yieldb,c (%)
O
O
8
886
966
1a
NO2
1h
O
NHAc
NHAc
O
NHAc
2
3
5
5
998
9
11
6
956
NO2
1i
Cl
1b
O
NHAc
NHAc
98
10
85
O
Br
1c
1j
O
O
NHAc
O
O
4
5
6
7
5
6
9410
11
12
13
12
9
83
97
96
Cl
OMe
1d
1k
NHAc
NHAc
O
NHCOPh
NHCOPh
OMe
OMe
98
1l
1e
O
O
OMe
OMe
96
8
Cl
OMe
NHAc
1m
1f
O
NHCOPh
O
7
12
906
14
12
92
NO2
O2N
1g
1n
a
All the products were fully characterized by usual spectroscopic techniques and their data were compared with authentic data.
Yields were calculated just after aqueous work up.
Corresponding literature reference.
b
c

A. T. Khan et al. / Tetrahedron 63 (2007) 5593–5601
5595
aldehydes such as cinnamaldehyde also reacts under the same
experimental conditions and provided the desired product (Ta-
ble 1, entry 10) without any difficulty. A 1,3-diketone, namely
benzoylacetone, wastreatedunderthe sameexperimentalcon-
ditions to provide b-acetamido diketones with poor diastereo-
selectivity. Next, by using benzonitrile in place of acetonitrile,
avarietyofaldehydesweretransformedtotheircorresponding
b-benzamido ketones in excellent yields (Table 1, entries 12–
14). This clearly demonstrates that in this reaction, the alkyl/
aryl nitrile acts as a nucleophile.
b-acetamido keto ester (Table 3). All these products were
fully characterized by recording IR, 1H NMR, and elemental
analysis.
To further confirm the formation of these alkenes and to
know the geometry of the substituents on the double bond,
Table 3. FeCl3$6H2O catalyzed Knoevenagel products for nitro benzalde-
hydes along with trace multi-component products
O
CHO
O
O
.
FeCl3 6H2O (10 mol%)
+
R1
R2
CH3CN, CH3COCl, rt
To extend the preparative utility and generality of this multi-
component reaction, a variety of aromatic aldehydes were
treated with methyl acetoacetate or ethyl benzoyl acetoace-
tate under the same experimental conditions, and the corre-
sponding b-acetamido/benzamido keto esters were obtained
in good yields with moderate to good diastereoselectivities.
These b-acetamido esters are useful precursor for the synthe-
sis of b-aryl homoisothreonine derivatives, which can be
used for the preparation of dipeptide isoesters by incorpora-
tion with an amino acid residue. The ratio of syn:anti diaste-
reomers was determined from the 1H NMR spectrum of the
crude reaction mixture. The ratio of diastereomers differed
with substitution on the aromatic ring (Table 2).
O
OMe
O2N
O2N
Entry
Producta
Yieldb (%)
NO2
O
1
2
81
80
82
O
OMe
3a
O
O
OMe
NO2
3b
O
Interestingly, during the course of our study we have noticed
that when the aldehyde contains a nitro group either at the
ortho, meta or para positions, and is treated with a b-keto es-
ter under the same experimental conditions, it gives only the
Knoevenagel condensation product instead of our expected
3
O2N
O
OMe
3c
a
All the products were characterized by usual spectroscopic analysis.
Isolated yield.
b
Table 2. FeCl3$6H2O catalyzed multi-component reaction for the preparation of b-acetamido esters
ROCHN
R1
O
O
ROCHN
O
O
CHO
.
O
O
FeCl3 6H2O (10 mol %)
R2
R2
+
+
RCN, CH3COCl, rt
R1
R2
R1
X
X
X
Syn
Anti
Entry
1
Product
Yielda,c (%)
syn:antib
Entry
Product
Yielda (%)
syn:antib
AcHN
O
AcHN
O
MeO
OMe
815
26:74
5
6
84
25:75
OMe
MeO
O
O
OMe
2a
2e
AcHN
O
AcHN
O
805
27:73
46:54
78
80
98:2
95:5
OMe
OEt
O
2
3
Cl
O
O
Ph
2f
2b
AcHN
AcHN
O
MeO
MeO
OEt
825
7
8
OMe
OMe
O
Ph
2g
MeO
MeO
O
OMe
2c
AcHN
O
PhCOHN
O
OMe
4
86
5:95
85
71:29
O
O
2h
OMe
2d
a
Yields were calculated without further purification.
The syn:anti ratio was determined from 1H NMR spectrum of crude reaction mixture.
Corresponding literature reference.
b
c

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A. T. Khan et al. / Tetrahedron 63 (2007) 5593–5601
treated with 10 mol % of the catalyst in acetonitrile as
solvent, and the corresponding b-acetamido ketone was
obtained in 80% yield under the same experimental condi-
tions. This clearly demonstrates the working hypothesis
that the reaction goes via an aldol reaction followed by
acetylation and subsequent nucleophilic displacement by
the alkyl/aryl nitrile to get the desired product as shown
in Scheme 4.
Next, the aldol product 4 was prepared following a literature
procedure using proline as an organo catalyst,24 and acety-
lated by our self developed BDMS method25 to get the
product 4a. Subsequently, the compound 4a was treated
separately with acetonitrile under the same experimental
conditions using 10 mol % FeCl3$6H2O as a catalyst. Inter-
estingly, after 12 h of stirring, a,b-unsaturated ketone 4c was
isolated in 98% yield instead of the desired b-acetamido
ketone 4b as shown in Scheme 3. Similarly, in Table 3 we
have noted that nitro substituted aldehydes react with methyl
acetoacetate and provide the Knoevenagel condensation
products under the experimental conditions. These studies
lead us to the conclusion that when aliphatic ketones or
keto esters react with nitro substituted aldehydes, the inter-
mediate acetylated aldol products (e.g., 4a) prefer a-H
elimination to provide a,b-unsaturated ketones to the forma-
tion of desired acetamido ketone by nucleophilic substitu-
tion by alkyl or aryl nitrile. This may be attributed to the
electronic effect, i.e., the electron withdrawing nature of
the substituent as well as, the stability of the elimination
products. Later, the Knoevenagel product 3b was treated fur-
ther with acetonitrile and acetyl chloride in the presence of
10 mol % catalyst and kept stirring. No detectable amount
of the desired b-acetamido keto ester was found, even after
stirring for 12 h. Thus it is clear that these unsaturated
ketones are more stable compared to the corresponding
b-acetamido ketones.
Figure 1. ORTEP plot of compound 3b.
the product 3b was recrystallized from ethyl acetate–hexane
and a single crystal XRD was recorded. It shows the (Z)-
configuration of the alkene as depicted in Figure 1.
Although the exact explanation of this anomaly is yet to be
determined, we assumed that due to electronic effects, i.e.,
electron withdrawing nature of the nitro group, it provides
the Knoevenagel condensation alkenes.
Next we turned our attention to study the mechanistic as-
pect of this multi-component reaction. Thus, the reaction
of 4-chlorobenzaldehyde with acetophenone was chosen
as a model reaction for this study. In the absence of acetyl
chloride, the reaction failed to provide the desired product,
which clearly indicates that it plays a vital role in this
reaction, although not directly involved in the final product.
Then the same reaction was tried using oxalyl chloride,
instead of acetyl chloride, and the reaction was also unsuc-
cessful. From this observation, it is clear that the chloride
ion does not have any role in the above transformation.
Similarly, the same reaction was carried out in the absence
of acetonitrile using dichloromethane as a solvent, and the
corresponding b-acetoxy ketone was obtained in 60% yield
after 3 h of stirring at room temperature. Consequently, this
b-acetoxy ketone as shown in Scheme 2 was once again
Next to exemplify that acetyl chloride is not incorporated in
the final product and acetonitrile itself is the N-donor and
nucleophile (i.e., it follows the Ritter reaction pathway),
we tried the reaction of 4-chlorobenzaldeyde under similar
experimental conditions using benzonitrile (1.5 equiv) in-
stead of acetonitrile (Table 1, entry 13). The formation of
benzamide clearly indicates that in this reaction nitrile acts
not only as a solvent but also as a nitrogen donor. Therefore,
O
OAc
.
FeCl3 6H2O (10 mol %)
CH2Cl2, AcCl, rt, 3 h
Cl
O
.
FeCl3 6H2O (10 mol %)
No reaction
CH3CN, rt, 12 h
.
FeCl3 6H2O (cat.)
CH3CN, rt, 3 h
.
FeCl3 6H2O (10 mol %)
+
No reaction
O
CH3CN, (COCl)2, rt, 12 h
CHO
NHAc
.
Cl
FeCl3 6H2O (10 mol %)
CH3CN, AcCl, rt, 5 h
Cl
Scheme 2.

A. T. Khan et al. / Tetrahedron 63 (2007) 5593–5601
OH
5597
O
OAc O
CHO
O
i
ii
+
O2N
O2N
O2N
4a
4
iii
O
O
NHAc
O2N
4b
NO2
4c
0 %
98%
Scheme 3. Reagents: (i) proline (20 mol %), H2O; (ii) BDMS (5 mol %), Ac2O; (iii) FeCl3$6H2O (10 mol %), CH3CN, CH3COCl.
1
the most probable mechanism for this reaction is illustrated
in Scheme 4.
spectrophotometer. H NMR spectra and 13C NMR spectra
were recorded on a Varian 400 MHz spectrometer in
CDCl3 or DMSO, d6 using TMS as an internal reference.
Elemental analyses were carried out in a Perkin Elmer 2400
automatic carbon, hydrogen, nitrogen, and sulfur analyzer.
Column chromatographic separations were done on SRL
silica gel (60–120 mesh).
Fe3+
O
O
O
OAc
O
CH3COCl
H
X
X
4.2. General procedure for the preparation of b-acet-
amido/benzamido ketones or keto esters
CH3CN
To a stirred solution of aldehyde (2 mmol) and acetophe-
none/methyl acetoacetate (2 mmol) in acetonitrile (3 mL)
or benzonitrile (3 mmol) were added acetyl chloride
(3 mmol) and FeCl3$6H2O (0.2 mmol) and the reaction
stirred at room temperature. The progress of the reaction
was monitored by TLC, and after completion of the reaction,
crushed (50 mL) ice was added to the reaction mixture and
stirred thoroughly. On solidification, the products were
filtered off and dried to get the corresponding b-acetamido
ketones. For all the substrates of Table 2, the reactions
were stirred for 12 h, then 50 mL of water was added. The
mixture was extracted with ethyl acetate (3ꢀ20 mL),
washed with water (3ꢀ20 mL), dried over Na2SO4, and
the solvent was removed using a rotary evaporator. The
crude mixture was recrystallized from ethyl acetate–hexane
and the solid product (mixture of diastereomers) was
isolated. The solid products were recrystallized from the
mixture of solvents (ethyl acetate–hexane) and fully charac-
terized by recording IR, NMR, and elemental analysis.
NHAc
O
N=CCH3
H2O
X
X
Scheme 4. Probable mechanism of iron(III) chloride-catalyzed multi-com-
ponent reactions for the preparation of b-acetamido carbonyl compounds.
3. Conclusion
In summary, we have devised a new synthetic methodology
using FeCl3$6H2O, a cheap, readily available, and efficient
catalyst for the one-pot synthesis of b-acetamido carbonyl
compounds. In the case of nitro aldehydes, the reaction
with methyl acetoacetate provides a,b-unsaturated ketones
instead of the expected b-acetamido carbonyl compounds.
The simplicity of the present protocol, high yields, and
efficiency of the catalyst are the key features of this present
protocol. Due to the low cost and ready availability of the
reagent FeCl3$6H2O, we prefer this protocol than our earlier
reported method.14 In addition we have presented a thorough
study on the mechanistic aspect of this multi-component
reaction in this article. Thus the present method will be
useful for the facile preparation of b-acetamido ketones
and keto esters.
4.2.1. N-(3-Oxo-1,3-diphenyl-propyl) acetamide (1a).6
Yield 88% (470.0 mg), white crystal (EtOAc–hexane), mp
103–105 ꢁC (lit.6 mp 102–104 ꢁC) [Found: C, 76.49; H,
6.39; N, 5.19. C17H17NO2 requires C, 76.38; H, 6.41; N,
5.24%]; nmax (KBr): 3278, 3099, 2925, 1682, 1646, 1556,
1447, 1372, 1195, 990, 750 cmꢂ1; dH (400 MHz, CDCl3)
2.01 (3H, s, COMe), 3.43 (1H, dd, J 6.0, 16.8 Hz, CH2),
3.75 (1H, dd, J 5.2, 16.8 Hz, CH2), 5.53–5.57 (1H, m,
CH), 6.68 (1H, d, J 7.6 Hz, NH), 7.19–7.30 (5H, m, Ph),
7.43 (2H, t, J 8.0 Hz, Ph), 7.55 (1H, t, J 7.6 Hz, Ph), 7.88
(2H, d, J 8.0 Hz, Ph); dC (100 MHz, CDCl3) 23.6, 43.2,
49.9, 126.6, 127.7, 128.3, 128.9, 133.7, 136.4, 140.7,
169.3, 198.3.
4. Experimental
4.1. General
All reagents were of commercial quality and were used as
received. Solvents were dried and purified using standard
techniques. Melting points were recorded on a Buchi
B-545 melting point apparatus and are uncorrected. IR
spectra were recorded in KBr on a Nicolet Impact 410
4.2.2. N-[1-(4-Chlorophenyl)-3-oxo-3-phenyl-propyl]
acetamide (1b).8 Yield 99% (597.0 mg), white crystal

5598
A. T. Khan et al. / Tetrahedron 63 (2007) 5593–5601
(EtOAc–hexane), mp 146 ꢁC (lit.8 mp 146–148 ꢁC) [Found:
C, 67.53; H, 5.28; N, 4.72. C17H16ClNO2 requires C, 67.66;
H, 5.34; N, 4.64%]; nmax (KBr): 3291, 2329, 1687, 1647,
1547, 1445, 1349, 1229, 1009, 754 cmꢂ1; dH (400 MHz,
CDCl3) 2.01 (3H, s, COMe), 3.41 (1H, dd, J 6.0, 16.8 Hz,
CH2), 3.73 (1H, dd, J 5.2, 17.2 Hz, CH2), 5.50–5.55 (1H,
m, CH), 6.74 (1H, d, J 7.2 Hz, NH), 7.25 (4H, d, J 4.4 Hz,
Ph), 7.44 (2H, t, J 8.0 Hz, Ph), 7.56 (1H, t, J 7.6 Hz, Ph),
7.87 (2H, d, J 8.4 Hz, Ph); dC (100 MHz, CDCl3) 23.0,
43.2, 49.4, 128.1, 128.3, 128.9, 133.6, 133.9, 140.0, 142.0,
148.0, 165.0, 198.7.
J 5.2, 16.8 Hz, CH2), 3.76 (3H, s, OMe), 3.78 (6H, s,
2ꢀOMe), 5.44 (1H, q, J 7.6 Hz, CH), 6.52 (2H, s, Ph),
6.67 (1H, d, J 7.6 Hz, NH), 7.43 (2H, t, J 7.6 Hz, Ph), 7.55
(1H, t, J 7.2 Hz, Ph), 7.88 (2H, d, J 8.0 Hz, Ph); dC
(100 MHz, CDCl3) 23.7, 43.4, 50.7, 56.3, 60.9, 103.9,
128.3, 128.9, 133.8, 136.8, 136.9, 153.5, 156.2, 169.5, 199.4.
4.2.7. N-[1-(2-Nitrophenyl)-3-oxo-3-phenyl-propyl] acet-
amide (1g).6 Yield 90% (560.0 mg), white solid, mp 190–
191 ꢁC (lit.6 mp 186–188 ꢁC) [Found: C, 65.49; H, 5.23;
N, 8.88. C17H16N2O4 requires C, 65.38; H, 5.16; N,
8.97%]; nmax (KBr): 3326, 2379, 1686, 1651, 1544, 1517,
1357, 1337, 1059, 682 cmꢂ1; dH (400 MHz, CDCl3) 2.00
(3H, s, COMe), 3.63 (1H, dd, J 5.6, 16.8 Hz, CH2), 3.71
(1H, dd, J 6.4, 17.2 Hz, CH2), 5.93–5.97 (1H, m, CH),
7.07 (1H, d, J 5.6 Hz, NH), 7.39 (1H, t, J 8.0 Hz, Ph), 7.46
(2H, t, J 8.0 Hz, Ph), 7.57 (2H, t, J 7.6 Hz, Ph), 7.71 (1H,
d, J 8.0 Hz, Ph), 7.92 (2H, d, J 7.2 Hz), 7.94 (1H, d, J 6.8,
Ph); dC (100 MHz, CDCl3) 23.5, 42.4, 47.7, 125.3, 128.5,
128.6, 129.0, 130.1, 133.7, 134.1, 136.5, 137.1, 148.7,
169.5, 198.5.
4.2.3. N-[1-(4-Bromophenyl)-3-oxo-3-phenyl-propyl]
acetamide (1c). Yield 98% (678.0 mg), white crystal
(EtOAc–hexane), mp 148–150 ꢁC [Found: C, 58.85; H,
4.70; N, 4.12. C17H16BrNO2 requires C, 58.98; H, 4.66; N,
4.05%]; nmax (KBr): 3285, 2923, 1684, 1651, 1550, 1374,
1292, 1006, 757 cmꢂ1; dH (400 MHz, CDCl3) 2.02 (3H, s,
COMe), 3.40 (1H, dd, J 6.0, 17.2 Hz, CH2), 3.72 (1H, dd,
J 5.2, 16.8 Hz, CH2), 5.49–5.51 (1H, m, CH), 6.73 (1H, d,
J 6.8, NH), 7.19 (2H, d, J 8.4 Hz, Ph), 7.40 (2H, d, J
8.4 Hz, Ph), 7.44 (2H, d, J 8.0 Hz, Ph), 7.55 (1H, t, J
7.2 Hz, Ph), 7.87 (2H, d, J 7.2 Hz, Ph); dC (100 MHz,
CDCl3) 23.7, 42.9, 49.4, 128.3, 128.4, 129.0, 131.9, 134.0,
136.2, 140.2, 166.5, 196.5.
4.2.8. N-[1-(3-Nitrophenyl)-3-oxo-3-phenyl-propyl] acet-
amide (1h).6 Yield 96% (593.0 mg), white solid, mp 139–
140 ꢁC (lit.10 mp 139–140 ꢁC) [Found: C, 65.29; H, 5.22;
N, 8.88. C17H16N2O4 requires C, 65.38; H, 5.16; N,
8.97%]; nmax (KBr): 3306, 1693, 1644, 1545, 1522, 1347,
983, 684 cmꢂ1; dH (400 MHz, CDCl3) 2.08 (3H, s,
COMe), 3.51 (1H, dd, J 5.6, 17.6 Hz, CH2), 3.79 (1H, dd,
J 5.2, 17.6 Hz, CH2), 5.62–5.67 (1H, m, CH), 6.91 (1H, d,
J 7.6 Hz, NH), 7.42–7.49 (3H, m, Ph), 7.57 (1H, t, J
7.6 Hz, Ph), 7.68 (1H, d, J 7.6 Hz, Ph), 7.87 (2H, d, J
7.6 Hz, Ph), 8.06 (1H, d, J 6.8 Hz, Ph), 8.19 (1H, s, Ph);
dC (100 MHz, CDCl3) 23.6, 42.9, 49.3, 121.5, 122.6,
128.3, 129.1, 129.8, 130.8, 133.1, 134.2, 136.4, 143.7,
169.9, 198.3.
4.2.4. N-[1-(4-Methoxyphenyl)-3-oxo-3-phenyl-propyl]
acetamide (1d).10 Yield 94% (560.0 mg), white crystal
(EtOAc–hexane), mp 110–111 ꢁC (lit.10 mp 110–112 ꢁC)
[Found: C, 72.59; H, 6.49; N, 4.79. C18H19NO3 requires C,
72.71; H, 6.44; N, 4.71%]; nmax (KBr): 3301, 2928, 1688,
1648, 1545, 1372, 1238, 1033, 754 cmꢂ1; dH (400 MHz,
CDCl3) 2.0 (3H, s, COMe), 3.39 (1H, dd, J 6.4, 16.8 Hz,
CH2), 3.72 (1H, dd, J 5.2, 17.2 Hz, CH2), 3.74 (3H, s,
OMe), 5.46–5.51 (1H, m, CH), 6.57 (1H, d, J 8.0 Hz, NH),
6.81 (2H, d, J 8.4 Hz, Ph), 7.23 (2H, d, J 8.0 Hz, Ph), 7.42
(2H, t, J 7.6 Hz, Ph), 7.54 (1H, t, J 7.2 Hz, Ph), 7.89 (2H,
d, J 7.2 Hz, Ph); dC (100 MHz, CDCl3) 23.6, 43.5, 49.7,
55.4, 114.2, 127.9, 128.3, 128.9, 133.1, 133.7, 136.7,
158.9, 169.7, 198.8.
4.2.9. N-[1-(4-Nitrophenyl)-3-oxo-3-phenyl-propyl] acet-
amide (1i).6 Yield 95% (593.0 mg), yellow crystalline solid,
mp 153 ꢁC (lit.10 mp 154 ꢁC) [Found: C, 65.29; H, 5.23; N,
8.99. C17H16N2O4 requires C, 65.38; H, 5.16; N, 8.97%];
nmax (KBr): 3306, 1696, 1646, 1595, 1537, 1350, 988,
755 cmꢂ1; dH (400 MHz, CDCl3) 2.10 (3H, s, COMe), 3.51
(1H, dd, J 5.6, 17.6 Hz, CH2), 3.81 (1H, dd, J 5.2, 17.6 Hz,
CH2), 5.65–5.67 (1H, m, CH), 6.96 (1H, d, J 8.0 Hz, NH),
7.47 (2H, t, J 8.0 Hz, Ph), 7.51 (2H, d, J 8.8 Hz, 2H, Ph),
7.60 (1H, t, J 7.2 Hz, Ph), 7.89 (2H, d, J 7.2 Hz, Ph), 8.17
(2H, d, J 8.8 Hz, Ph); dC (100 MHz, CDCl3) 23.5, 42.6,
49.2, 123.7, 127.2, 127.9, 128.7, 131.0, 133.9, 136.0,
138.4, 169.5, 197.8.
4.2.5. N-[1-(3,4-Dimethoxyphenyl)-3-oxo-3-phenyl-pro-
pyl] acetamide (1e). Yield 98% (640.0 mg), brownish solid,
mp 118–119 ꢁC [Found: C, 69.58; H, 6.40; N, 4.37.
C19H21NO4 requires C, 69.71; H, 6.47; N, 4.28%]; nmax
(KBr): 3247, 3076, 2917, 2846, 1681, 1637, 1519, 1462,
1253, 1026, 751 cmꢂ1; dH (400 MHz, CDCl3) 2.01 (3H, s,
COMe), 3.39 (1H, dd, J 6.4, 16.8 Hz, CH2), 3.72 (1H, dd,
J 5.2, 16.4 Hz, CH2), 3.81 (3H, s, OMe), 3.82 (3H, s,
OMe), 5.45–5.50 (1H, m, CH), 6.58 (1H, d, J 8.0 Hz, NH),
6.76 (1H, d, J 8.0 Hz, Ph), 6.83 (2H, s+d, J 8.0 Hz, Ph),
7.43 (2H, t, J 7.6 Hz, Ph), 7.55 (1H, t, J 7.6 Hz, Ph), 7.89
(2H, d, J 7.2 Hz, Ph); dC (100 MHz, CDCl3) 23.7, 43.4,
50.1, 56.1, 110.5, 111.3, 118.3, 128.3, 128.9, 133.6, 133.7,
149.2, 169.6, 199.0.
4.2.10. N-[1-(4-Styryl)-3-oxo-3-phenyl-propyl] acet-
amide (1j). Yield 85% (497.0 mg), light yellow solid, mp
120–121 ꢁC [Found: C, 77.68; H, 6.45; N, 4.83.
C19H19NO2 requires C, 77.79; H, 6.53; N, 4.77%]; nmax
(KBr): 3291, 3065, 2928, 1687, 1648, 1635, 1547, 1445,
1366, 1083, 751 cmꢂ1; dH (400 MHz, CDCl3) 2.04 (3H, s,
COMe), 3.35 (1H, dd, J 5.6, 17.6 Hz, CH2), 3.53 (1H, dd,
J 4.4, 17.6 Hz, CH2), 5.09–5.13 (1H, m, CH), 6.33 (1H,
dd, J 6.8, 16.0 Hz, CH]), 6.54 (1H, d, J 15.6 Hz, CH]),
7.20 (1H, d, J 6.8 Hz, NH), 7.25 (2H, t, J 6.8 Hz, Ph), 7.29
(3H, d, J 7.2 Hz, Ph), 7.46 (2H, t, J 7.6 Hz, Ph), 7.57 (1H,
t, J 7.6 Hz, Ph), 7.93 (2H, d, J 7.2 Hz, Ph); dC (100 MHz,
4.2.6. N-[1-(3,4,5-Trimethoxyphenyl)-3-oxo-3-phenyl-
propyl] acetamide (1f). Yield 96% (685.0 mg), white solid,
mp 168–169 ꢁC [Found: C, 67.34; H, 6.42; N, 3.99.
C20H23NO5 requires C, 67.21; H, 6.49; N, 3.92%]; nmax
(KBr): 3276, 2928, 1688, 1648, 1592, 1458, 1339, 1246,
1001, 754 cmꢂ1; dH (400 MHz, CDCl3) 2.01 (3H, s,
COMe), 3.37 (1H, dd, J 6.0, 16.8 Hz, CH2), 3.69 (1H, dd,

A. T. Khan et al. / Tetrahedron 63 (2007) 5593–5601
5599
CDCl3) 23.8, 42.8, 48.3, 126.7, 127.9, 128.3, 128.6, 128.7,
128.9, 1301.7, 133.9, 169.5, 199.7.
128–130 ꢁC (lit.5 mp 129–131 ꢁC) [Found: C, 63.74; H,
6.45; N, 5.43. C14H17NO4 requires C, 63.87; H, 6.51; N,
5.32%]; nmax (KBr): 3329, 3049, 2961, 1747, 1717, 1643,
1528, 1451, 1371, 1037, 754 cmꢂ1. Data for the major iso-
mer (anti): dH (400 MHz, CDCl3) 1.99 (3H, s, COMe),
2.10 (3H, s, COMe), 3.69 (3H, s, OMe), 4.07 (1H, d, J
5.6 Hz, CH), 5.73 (1H, dd, J 5.6, 9.2 Hz, CH), 6.91 (1H, d,
J 8.4 Hz, NH), 7.23–7.31 (5H, m, Ph); dC (100 MHz,
CDCl3) 23.5, 31.1, 52.5, 53.0, 62.5, 126.6, 128.0, 128.9,
139.3, 166.1, 169.9, 203.8.
4.2.11. N-[1-(4-Chlorophenyl)-2-acetyl-3-oxo-3-phenyl-
propyl] acetamide (1k). Yield 83% (571.0 mg), white solid
(mixture of diastereomers): (syn:anti¼40:60), mp 172–
174 ꢁC [Found: C, 66.49; H, 5.21; N, 4.18. C19H18NClO3 re-
quires C, 66.38; H, 5.28; N, 4.07%]; nmax (KBr): 3301, 1704,
1688, 1648, 1527, 1370, 1087 cmꢂ1; Data for the major iso-
mer (anti): dH (400 MHz, CDCl3) 1.95 (3H, s, COMe), 2.13
(3H, s, COMe), 5.05 (1H, d, J 7.6 Hz, CH), 5.85 (1H, t, J
8.4 Hz, CH), 6.57 (1H, d, J 8.4 Hz, NH), 7.23 (4H, d, J
6.4 Hz, Ph), 7.47 (2H, t, J 7.2 Hz, Ph), 7.59 (1H, t,
J 8.8 Hz, Ph), 7.73 (1H, d, J 8.0 Hz, Ph), 7.90 (1H, d, J
8.4 Hz, Ph); dC (100 MHz, CDCl3) 23.5, 29.2, 52.4, 66.7,
128.5, 128.8, 129.2, 129.3, 133.9, 134.5, 135.9, 138.5,
169.8, 193.8, 204.0.
4.2.16. Methyl 2-acetyl-3-acetamido-3-(p-chlorophenyl)
propionate (2b).5 Yield 80% (477.0 mg), white solid (mix-
ture of diastereomers), mp 131–133 ꢁC (lit.5 mp 130–
132 ꢁC) [Found: C, 56.60; H, 5.36; N, 4.82. C14H16ClNO4
requires C, 56.49; H, 5.42; N, 4.71%]; nmax (KBr): 3324,
1744, 1714, 1646, 1541, 1486, 1371, 1091, 724 cmꢂ1
.
Data for the major isomer (anti): dH (400 MHz, CDCl3)
1.99 (3H, s, COMe), 2.13 (3H, s, COMe), 3.70 (3H, s,
OMe), 4.04 (1H, d, J 5.6 Hz, CH), 5.68 (1H, dd, J 5.6,
9.2 Hz, CH), 6.94 (1H, d, J 8.4 Hz, NH), 7.20 (2H, d, J
8.8 Hz, Ph), 7.25 (2H, d, J 8.0 Hz, Ph); dC (100 MHz,
CDCl3) 23.5, 31.0, 52.0, 53.1, 62.4, 128.2, 129.1, 133.9,
138.0, 167.8, 169.9, 203.8.
4.2.12. N-(3-Oxo-1,3-diphenyl-propyl) benzamide (1l).
Yield 97% (639.0 mg), yellowish solid, mp 153–154 ꢁC
[Found: C, 80.33; H, 5.76; N, 4.31. C22H19NO2 requires C,
80.22; H, 5.81; N, 4.25%]; nmax (KBr): 3306, 3062, 1681,
1634, 1599, 1488, 1357, 981, 754 cmꢂ1; dH (400 MHz,
CDCl3) 3.52 (1H, dd, J 6.0, 16.4 Hz, CH2), 3.87 (1H, dd, J
4.8, 16.8 Hz, CH2), 5.73–5.78 (1H, m, CH), 7.22 (1H, t, J
7.2 Hz, Ph), 7.30 (2H, t, J 7.6 Hz, Ph), 7.37–7.45 (5H, m,
Ph), 7.49 (2H, t, J 7.2 Hz, Ph), 7.55 (1H, t, J 7.2 Hz, Ph),
7.60 (1H, d, J 8.0 Hz, Ph), 7.82 (2H, d, J 8.0 Hz, Ph), 7.90
(2H, d, J 8.0 Hz, Ph); dC (100 MHz, CDCl3) 43.1, 50.4,
126.6, 127.2, 127.6, 128.3, 128.7, 128.8, 128.9, 131.8,
133.8, 134.4, 136.7, 141.1, 166.9, 199.3.
4.2.17. Methyl 2-acetyl-3-acetamido-3-(p-methoxy-
phenyl) propionate (2c).5 Yield 82% (480.0 mg), light yel-
low solid (mixture of diastereomers), mp 140–143 ꢁC (lit.5
mp 142–144 ꢁC) [Found: C, 61.53; H, 6.48; N, 4.86.
C15H19NO5 requires C, 61.42; H, 6.53; N, 4.77%]; nmax
(KBr): 3335, 2967, 1739, 1714, 1648, 1602, 1517, 1434,
1369, 1028, 587 cmꢂ1. Data for the major isomer (anti):
dH (400 MHz, CDCl3) 1.97 (3H, s, COMe), 2.14 (3H, s,
COMe), 3.68 (3H, s, OMe), 3.76 (3H, s, OMe), 3.86 (1H,
d, J 6.0 Hz, CH), 5.61 (1H, dd, J 6.0, 9.2 Hz, CH), 6.81
(2H, d, J 8.0 Hz, Ph), 6.98 (1H, d, J 8.4 Hz, NH), 7.18
(2H, d, J 8.4 Hz, Ph); dC (100 MHz, CDCl3) 23.3, 30.7,
52.8, 55.2, 55.4, 62.7, 127.7, 131.2, 131.7, 131.9, 160.3,
169.5, 187.8.
4.2.13. N-[1-(4-Chlorophenyl)-3-oxo-3-phenyl-propyl]
benzamide (1m). Yield 96% (699.0 mg), yellow solid,
mp 180–182 ꢁC [Found: C, 72.74; H, 4.93; N, 3.93.
C22H18ClNO2 requires C, 72.63; H, 4.99; N, 3.85%]; nmax
(KBr): 3276, 2928, 2372, 1683, 1641, 1542, 1490, 1362,
1087, 689 cmꢂ1; dH (400 MHz, CDCl3) 3.52 (1H, dd, J
5.6, 17.2 Hz, CH2), 3.86 (1H, dd, J 4.8, 17.2 Hz, CH2),
5.71–5.75 (1H, m, CH), 7.28 (2H, d, J 8.4 Hz, Ph), 7.35
(2H, d, J 8.4 Hz, Ph), 7.46 (2H, t, J 7.6 Hz, Ph), 7.47 (2H,
t, J 7.6 Hz, Ph), 7.53 (1H, t, J 7.2 Hz, Ph), 7.59 (1H, t, J
7.2 Hz, Ph), 7.69 (1H, d, J 8.0 Hz, NH), 7.84 (2H, d, J
7.6 Hz, Ph), 7.91 (2H, d, J 8.0 Hz, Ph); dC (100 MHz,
CDCl3) 42.6, 49.6, 127.0, 127.9, 128.1, 128.6, 128.8,
131.7, 133.1, 133.8, 136.4, 139.5, 166.7, 198.9.
4.2.18. Methyl 2-acetyl-3-acetamido-3-(dimethoxy-
phenyl) propionate (2d). Yield 86% (556.0 mg), white
solid (mixture of diastereomers), mp 125–127 ꢁC [Found:
C, 59.55; H, 6.49; N, 4.42. C16H21NO6 requires C, 59.43;
H, 6.55; N, 4.33%]; nmax (KBr): 3331, 2928, 1745, 1718,
1648, 1542, 1458, 1372, 1023, 546 cmꢂ1. Data for the major
isomer (anti): dH (400 MHz, CDCl3) 1.98 (3H, s, COMe),
2.15 (3H, s, COMe), 3.68 (3H, s, OMe), 3.83 (3H, s,
OMe), 3.85 (3H, s, OMe), 4.03 (1H, d, J 6.0 Hz, CH), 5.66
(1H, dd, J 6.4, 9.2 Hz, CH), 6.78 (1H, s, Ph), 6.79 (2H, d,
J 7.6 Hz, Ph), 6.84 (1H, d, J 9.2 Hz, NH); dC (100 MHz,
CDCl3) 23.6, 30.9, 52.4, 53.0, 56.1, 63.0, 110.3, 111.3,
118.8, 131.9, 149.0, 149.2, 167.9, 169.7, 204.2.
4.2.14. N-[1-(4-Nitrophenyl)-3-oxo-3-phenyl-propyl]
benzamide (1n). Yield 92% (689.0 mg), solid, mp 142–
144 ꢁC [Found: C, 70.69; H, 4.80; N, 7.39. C22H18N2O4
requires C, 70.58; H, 4.85; N, 7.48%]; nmax (KBr): 3313,
3060, 2934, 1684, 1626, 1517, 1399, 1111, 688 cmꢂ1; dH
(400 MHz, CDCl3) 3.57 (1H, dd, J 4.4, 18.0 Hz, CH2),
3.90 (1H, dd, J 4.4, 16.8 Hz, CH2), 5.82–5.86 (1H, m,
CH), 7.46 (4H, t, J 7.6 Hz, Ph), 7.52 (1H, d, J 6.8 Hz,
NH), 7.55–7.59 (4H, m, Ph), 7.84 (2H, d, J 7.6 Hz, Ph),
7.89 (2H, d, J 7.6 Hz, Ph), 8.16 (2H, d, J 8.8 Hz, Ph); dC
(100 MHz, CDCl3) 42.7, 49.9, 124.1, 127.3, 127.7, 128.4,
128.9, 129.1, 132.2, 133.8, 134.3, 136.4, 147.2, 148.8,
167.0, 198.0.
4.2.19. Methyl 2-acetyl-3-acetamido-3-(trimethoxy-
phenyl) propionate (2e). Yield 84% (593.0 mg), brown
solid (mixture of diastereomers), mp 130–133 ꢁC [Found:
C, 57.89; H, 6.50; N, 4.09. C17H23NO7 requires C, 57.78;
H, 6.56; N, 3.96%]; nmax (KBr): 3326, 2928, 1747, 1718,
1683, 1651, 1592, 1458, 1339, 1003, 670 cmꢂ1. Data for
the major isomer (anti): dH (400 MHz, CDCl3) 2.00 (3H, s,
COMe), 2.16 (3H, s, COMe), 3.69 (3H, s, OMe), 3.78 (3H,
s, OMe), 3.82 (6H, s, 2ꢀOMe), 4.01 (1H, d, J 6.0 Hz,
4.2.15. Methyl 2-acetyl-3-acetamido-3-phenyl propio-
nate (2a).5 Yield 81% (426.0 mg), white solid, mp

5600
A. T. Khan et al. / Tetrahedron 63 (2007) 5593–5601
CH), 5.64 (1H, dd, J 5.6, 8.8 Hz, CH), 6.47 (2H, s, Ph), 6.90
(1H, d, J 8.8 Hz, NH); dC (100 MHz, CDCl3) 23.5, 31.1,
31.2, 52.9, 53.0, 56.3, 60.9, 62.8, 103.9, 135.1, 153.5,
153.6, 167.9, 169.8, 200.0.
mp 151–152 ꢁC (lit.26 mp 148 ꢁC) [Found: C, 57.72; H,
4.39; N, 5.71. C12H11NO5 requires C, 57.83; H, 4.45; N,
5.62%]; nmax (KBr): 3065, 1732, 1651, 1618, 1525, 1443,
1390, 1091, 735, 688 cmꢂ1; dH (400 MHz, CDCl3) 2.43
(3H, s, OMe), 3.87 (3H, s, OMe), 7.58 (1H, s, Ph), 7.59
(1H, t, J 7.6 Hz, Ph), 7.72 (1H, d, J 7.6 Hz, Ph), 8.25 (1H,
d, J 8.4 Hz, Ph), 8.29 (1H, s, ]CH); dC (100 MHz,
CDCl3) 27.0, 53.1, 123.9, 125.2, 130.2, 134.8, 135.2,
136.7, 138.6, 147.5, 168.0, 194.0.
4.2.20. Ethyl 2-benzoyl-3-acetamido-3-phenyl propio-
nate (2f). Yield 78% (529.0 mg), white solid (mixture of
diastereomers), mp 133–134 ꢁC [Found: C, 70.89; H, 6.29; N,
4.03. C20H21NO4 requires C, 70.78; H, 6.24; N, 4.13%];
nmax (KBr): 3311, 1724, 1691, 1651, 1597, 1352, 1097,
695, 543 cmꢂ1. Data for the major isomer (syn): dH
(400 MHz, CDCl3) 1.20 (3H, t, J 7.2 Hz, Me), 2.08 (3H, s,
Me), 4.18 (2H, q, J 7.2 Hz, OCH2), 4.98 (1H, d, J 4.0 Hz,
CH), 5.91 (1H, dd, J 4.0, 9.2 Hz, CH), 7.15 (1H, t, J
7.2 Hz, Ph), 7.22 (3H, m, Ph), 7.30 (2H, d, J 7.6 Hz, Ph),
7.40 (1H, t, J 7.6 Hz, Ph), 7.47 (1H, d, J 9.2 Hz, NH), 7.54
(1H, t, J 8.4 Hz, Ph), 7.79 (2H, d, J 8.4 Hz, Ph); dC
(100 MHz, CDCl3) 31.8, 41.8, 53.0, 53.3, 62.2, 126.6,
127.3, 128.0, 128.8, 129.0, 131.9, 134.2, 139.3.
4.2.25. Methyl 2-(p-nitrobenzylidene) acetoacetate (3c).
Yield 82% (408.0 mg), yellow crystalline solid (EtOAc–
hexane), mp 110–114 ꢁC [Found: C, 57.74; H, 4.40; N,
5.54. C12H11NO5 requires C, 57.83; H, 4.45; N, 5.62%];
nmax (KBr): 1736, 1659, 1624, 1599, 1440, 1349, 1042,
817, 537 cmꢂ1; dH (400 MHz, CDCl3) 2.43 (3H, s,
COMe), 3.82 (3H, s, OMe), 7.56 (2H, d, J 8.8 Hz, Ph),
7.59 (1H, s, ]CH), 8.23 (2H, d, J 8.8 Hz, Ph); dC
(100 MHz, CDCl3) 27.1, 53.1, 109.9, 124.2, 130.1, 138.7,
139.6, 148.1, 167.0, 194.1.
4.2.21. Ethyl 2-benzoyl-3-acetamido-3-(trimethoxy-
phenyl) propionate (2g). Yield 80% (687 mg), white solid
(mixture of diastereomers), mp 150–152 ꢁC [Found: C,
64.21; H, 6.39; N, 3.15. C23H27NO7 requires C, 64.32; H,
6.34; N, 3.26%]; nmax (KBr): 3306, 2931, 1729, 1686,
1648, 1592, 1456, 1370, 1001, 733 cmꢂ1. Data for the major
isomer (syn): dH (400 MHz, CDCl3) 1.21 (3H, t, J 7.2 Hz,
Me), 2.07 (3H, s, COMe), 3.74 (3H, s, OMe), 3.75 (6H, s,
2ꢀOMe), 4.17 (2H, q, J 7.2 Hz, OCH2), 4.93 (1H, d, J
4.0 Hz, CH), 5.80 (1H, dd, J 4.0, 8.8 Hz, CH), 6.49 (2H, s,
Ph), 7.41 (2H, t, J 8.0 Hz, Ph), 7.50 (1H, d, J 8.8 Hz, NH),
7.55 (1H, t, J 7.2 Hz, Ph), 7.77 (2H, d, J 7.2 Hz, Ph); dC
(100 MHz, CDCl3) 14.2, 23.6, 53.5, 56.3, 56.6, 60.9, 62.4,
104.3, 128.5, 129.1, 134.3, 135.4, 153.4, 167.0, 199.5.
Acknowledgements
T.P and L.H.C are thankful to IITG and CSIR, India, respec-
tively, for their research fellowships. Authors are also grate-
ful to the director, IITG for providing the general facilities to
carry out this work. We are also grateful to DST, Govt. of
India for providing single crystal XRD facility under FIST
programme.
References and notes
1. Menendez, J. C. Synthesis 2006, 2624.
4.2.22. Methyl 2-acetyl-3-benzamido-3-phenyl propio-
nate (2h). Yield 85% (553.0 mg), light yellow solid (mixture
of diastereomers), mp 151–153 ꢁC [Found: C, 70.25; H,
5.84; N, 4.39. C19H19NO4 requires C, 70.14; H, 5.89; N,
4.30%]; nmax (KBr): 3346, 2941, 1744, 1719, 1633, 1527,
1458, 1360, 1031, 700 cmꢂ1. Data for the major isomer
(syn): dH (400 MHz, CDCl3) 2.15 (3H, s, COMe), 3.71
(3H, s, OMe), 4.21 (1H, d, J 4.4 Hz, CH), 5.91 (1H, dd,
J 4.4, 9.6 Hz, CH), 7.30–7.32 (4H, m, Ph), 7.43 (2H, t, J
7.6 Hz, Ph), 7.49 (2H, d, J 7.6 Hz, Ph), 7.80 (2H, d, J
7.2 Hz, Ph), 7.88 (1H, d, J 9.6 Hz, NH); dC (100 MHz,
CDCl3) 30.1, 53.0, 53.3, 62.2, 126.6, 127.3, 128.0, 128.8,
129.0, 131.9, 134.2, 139.0, 166.9, 167.9, 204.5.
2. (a) Barluenga, J.; Viado, A. L.; Aguilar, E.; Fustero, S.; Olano,
B. J. Org. Chem. 1993, 58, 5972; (b) Enders, D.; Moser, M.;
Geibel, G.; Laufer, M. C. Synthesis 2004, 2040; (c)
Mukhopadhyay, M.; Bhatia, B.; Iqbal, J. Tetrahedron Lett.
1997, 38, 1083.
3. (a) Kobinata, K.; Uramoto, M.; Nishii, M.; Kusakabe, H.;
Nakamura, G.; Isono, K. Agric. Biol. Chem. 1980, 44, 1709;
(b) Daehn, U.; Hagenmaier, H.; Hoehne, H.; Koenig, W. A.;
Wolf, G.; Zaehner, H. Arch. Microbiol. 1976, 107, 249.
4. Dakin, H. D.; West, R. J. Biol. Chem. 1928, 78, 745.
5. Rao, I. N.; Prabhakaran, E. N.; Das, S. K.; Iqbal, J. J. Org.
Chem. 2003, 68, 4079 and references therein.
6. Bahulayan, D.; Das, S. K.; Iqbal, J. J. Org. Chem. 2003, 68,
5735.
4.2.23. Methyl 2-(o-nitrobenzylidene) acetoacetate (3a).
Yield 81% (404.0 mg), crystalline white solid (EtOAc–hex-
ane), mp 90–93 ꢁC (lit.27 mp 102 ꢁC) [Found: C, 57.71; H,
4.39; N, 5.74. C12H11NO5 requires C, 57.83; H, 4.45; N,
5.62%]; nmax (KBr): 3062, 2953, 1733, 1683, 1599, 1448,
1362, 1053, 736, 605 cmꢂ1; dH (400 MHz, CDCl3) 2.49
(3H, s, COMe), 3.61 (3H, s, OMe), 7.43 (1H, t, J 7.6 Hz,
Ph), 7.59 (1H, d, J 7.6 Hz, Ph), 7.69 (1H, t, J 7.6 Hz, Ph),
8.08 (1H, s, ]CH), 8.24 (1H, d, J 7.6 Hz, Ph); dC
(100 MHz, CDCl3) 26.3, 51.5, 124.3, 129.6, 129.8, 132.0,
133.3, 135.4, 139.8, 147.1, 166.9, 193.8.
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