One-pot preparation of β-amido ketones/esters in a three-component condensation reaction using magnesium hydrogensulfate as an effective and reusable catalyst

Article abstract of DOI:10.1139/V08-013

A one-pot, three-component condensation of an aryl aldehyde, an enolizable ketone or β-keto ester, acetyl chloride, and acetonitrile or benzonitrile in the presence of magnesium hydrogensulfate as an active, recoverable, and reusable green catalyst is des

Full text of DOI:10.1139/V08-013

376
One-pot preparation of ␤-amido ketones/esters in
a three-component condensation reaction using
magnesium hydrogensulfate as an effective and
reusable catalyst
Hamid Reza Shaterian, Asghar Hosseinian, and Majid Ghashang
Abstract: A one-pot, three-component condensation of an aryl aldehyde, an enolizable ketone or β-keto ester, acetyl
chloride, and acetonitrile or benzonitrile in the presence of magnesium hydrogensulfate as an active, recoverable, and
reusable green catalyst is described for the synthesis of β-amido ketones/esters at room temperature. The key features
of this methodology are simplicity, mild reaction conditions, and high to excellent yields.
Key words: multi-component reaction, magnesium hydrogensulfate, heterogeneous catalyst, β-amido ketone/ester, mild
conditions.
Résumé : On décrit une condensation monotope à trois composants dont un aldéhyde aromatique, une cétone ou un β-
cétoester énolisable et du chlorure d’acétyle, de l’acétonitrile ou du benzonitrile, en présence de sulfate acide de ma-
gnésium comme catalyseur vert actif, récupérable et réutilizable, pour réaliser la synthèse à la température ambiante la
synthèse de β-amidocétones et de β-amidoesters. Les caractéristiques principales de cette méthodologie sont sa simpli-
cité, des conditions réactionnelles douces et des rendements allant d’élevés à excellents.
Mots-clés : réaction à plusieurs composants, sulfate acide de magnésium, catalyseur hétérogène, β-amidocétones, β-ami-
doesters, conditions douces.
[Traduit par la Rédaction] Shaterian et al. 383
Introduction
heteropoly acid (16), sulfuric acid absorbed on silica gel
(17), Sc(OTf)3 (18), silica supported H3PW12O40 (19),
K5CoW12O40·3H2O (20), CeCl3·7H2O (21), ZnO (22), iodine
(23), sulfated zirconia (24), iron(III) chloride (25), and p-TSA
(26). Herein we wish to report an efficient method for the
synthesis of β-amido carbonyl compounds in high to excellent
yields by employing Mg(HSO4)2 as an active environmentally
friendly heterogeneous catalyst (Scheme 1). We believe that
our method is simple, mild, and rapid for the synthesis of the
mentioned compounds at room temperature (RT).
Today, with the emergence of high-speed parallel synthe-
sis, the multi-component reaction (MCR) is widely em-
ployed for the rapid assembly of arrays with high molecular
diversity (1). Due to their inherent simple experimental pro-
cedures and their one-pot character, they are perfectly suited
for automated synthesis. Thus, MCRs have attracted consid-
erable interest owing to their exceptional synthetic efficiency
(2–7).
β-Amido ketones are important building blocks and inter-
mediates in synthesis For example, they are important pre-
cursors of heterocyclic compounds (8), as well as of β-amino
alcohols, which are common units in both natural and syn-
thetic biologically or pharmacologically important com-
pounds (9). The reported one-pot syntheses of the title
compounds from aldehydes, enolizable ketones, acetyl chlo-
ride, and acetonitrile or benzonitrile are based on some
Lewis or Brønsted acid catalysts such as CoCl2 (10, 11),
Montmorillonite K-10 clay (12), silica sulfuric acid (13),
BiCl3 generated from BiOCl (14), ZrOCl2·8H2O (15),
Scheme 1. Synthesis of β-amido carbonyl compounds using
Mg(HSO4)2 as an active heterogeneous catalyst.
Received 6 December 2007. Accepted 13 January 2008.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 27 March 2008.
H.R. Shaterian,1 A. Hosseinian, and M. Ghashang.
Department of Chemistry, Faculty of Sciences, University of
Sistan and Baluchestan, Zahedan, Iran.
1Corresponding author (e-mail: hrshaterian@hamoon.usb.ac.ir).
Can. J. Chem. 86: 376–383 (2008)
doi:10.1139/V08-013
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Shaterian et al.
377
Table 1. Preparation of N-(3-oxo-1,3-diphenylpropyl)
acetamide in the presence of various amounts of
Mg(HSO4)2 at room temperature.
This catalyst is safe, easy to handle, environmentally be-
nign, presents fewer disposal problems, and is stable in reac-
tion media. Magnesium hydrogensulfate has been used in
some organic reactions, such as acetylation and formylation
of alcohols (27), cleavage of C=N (28), and oxidation of
thiols (29).
Mg(HSO4)2
(mol%)
Time
(h)
Yield
(%)a
Entry
5
10
15
20
30
1
2
3
4
5
8
5
3
2.5
2.5
50
60
75
89
91
Results and discussion
First, we optimized the amount of magnesium hydrogen-
sulfate as catalyst in the reaction among benzaldehyde,
acetophenone, acetyl chloride, and acetonitrile (Table 1).
The amount of magnesium hydrogensulfate was chosen to
be 20 mol%.
Thus, we continued preparation of β-amido ketones in an
optimum model experiment: aldehydes (1 equiv.), enolizable
ketone or β-keto ester (1 equiv.), acetyl chloride (0.5 mL),
and acetonitrile or benzonitrile (reactant, as well as solvent,
2 mL) in the presence of magnesium hydrogensulfate (20
mol%, Table 2).
As shown in Table 2, aromatic aldehydes and
acetophenone derivatives with both electron-withdrawing
and electron-donating substituents afforded to the corre-
sponding β-amido ketones without the formation of any side
products and in high to excellent yields at RT (Table 2, en-
tries 1–22). Phenolic-OH groups under present reaction con-
ditions were converted to acetate (-OAc) groups (Table 2,
entries 19, 20).
Under the optimized reaction conditions, by using
benzonitrile in place of acetonitrile, aldehydes were trans-
formed to their corresponding β-benzamido ketones in high
yields (Table 2, entries 2, 15).
aIsolated yields.
reusability of the catalyst was checked by the reaction of
benzaldehyde and acetophenone in the presence of acetyl
chloride and acetonitrile using 20 mol% of Mg(HSO4)2 at
RT. The results indicate that the catalyst can be used five
times without any loss of its activity (Table 4).
To show the merit of the present work in comparison with
reported results in the literature, we compared results of
magnesium hydrogensulfate with BiOCl (14), ZrOCl2·8H2O
(15), CeCl3·7H2O (21), ZnO (22), and I2 (23) in the synthe-
sis of β-acetamido ketone derivatives. As shown in Table 5,
magnesium hydrogensulfate can act as an effective catalyst
with respect to reaction times, yields, and the obtained prod-
ucts.
Conclusion
In summary, we have demonstrated a new and important
catalytic activity of magnesium hydrogensulfate as an inex-
pensive, commercially available, and reusable catalyst for
the synthesis of β-amido ketones/esters in high to excellent
yields under mild conditions at RT. The simple experimental
procedure combined with the easy work-up and high to ex-
cellent yields of products are strong features of the presented
method.
We also studied the multi-component reaction of aromatic
aldehydes with other enolizable ketones (methyl
acetoacetate, ethyl acetoacetate, and propiophenone) and
acetonitrile in the presence of acetyl chloride and
Mg(HSO4)2 as catalyst. In all cases, mixtures of syn and anti
diastereomers were obtained. The amount of syn and anti
1
products was determined by H NMR spectra, the coupling
Experimental
constant between H-2 and H-3 is 6–9 Hz for an anti isomer
and 2–5 Hz for a syn isomer (10-12, 26). As shown in Ta-
ble 3, anti diastereomers were found to be major products.
The conformational preference of these anti diastereomers
depend on the intramolecular H-bonding between the acidic
proton and the carbonyl oxygen This phenomenon was con-
firmed by Ghosh et al. (15) with the X-ray crystallographic
analysis data. Methyl and ethyl acetoacetate afforded the
corresponding β-acetamido esters and the anti/syn
diastereoselectivity further increased from 61:39 to 81:19
(Table 3).
In a typical experiment, after a period of time in which
the reaction was completed, the mixture was filtered and the
heterogeneous catalyst was recovered. Then, the residue so-
lution was poured into the cooled water until a solid crude
product was formed. In every experiment all of the magne-
sium hydrogensulfate was easily recovered from the reaction
mixture. The reusability of the catalysts is one of their most
important benefits and makes them useful for commercial
applications. Thus, the recovery and reusability of magne-
sium hydrogensulfate was investigated. The separated cata-
lyst can be reused after washing with CHCl3 and drying. The
All reagents were purchased from Merck and Sigma-
Aldrich and used without further purification. All yields re-
fer to isolated products after purification. Products were
characterized by comparison with authentic samples and by
1
spectroscopy data (IR, H NMR, 13C NMR spectra). The
NMR spectra were recorded on a Bruker Avance DEX 500
and 300 MHz instrument. The spectra were measured in
CDCl3 (and DMSO-d6) relative to TMS (0.00 ppm). Ele-
mental analyses for C, H, and N were performed using a
Heraeus CHN-O-Rapid analyzer. IR spectra were recorded
on a JASCO FT-IR 460plus spectrophotometer. Mass spectra
were recorded on a Agilent technologies 5973 network mass
selective detector (MSD) operating at an ionization potential
of 70 eV. Melting points were determined in open capillaries
with a BUCHI 510. TLC was performed on silica-gel Poly-
Gram SIL G/UV 254 plates.
Preparation of magnesium hydrogensulfate
A 500 mL suction flask was equipped with a constant-
pressure dropping funnel. A gas outlet was connected to a
vacuum system through an adsorbing solution (water) and an
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Can. J. Chem. Vol. 86, 2008
Table 2. Preparation of β-amido ketones from aldehydes and acetophenone derivatives in the presence
of acetyl chloride and acetonitrile or benzonitrile catalyzed using Mg(HSO4)2 at room temperature.
1
alkali trap. Anhydrous magnesium chloride (47.6 g, 0.5 mol)
was charged into the flask and concentrated sulfuric acid
(98.07 g, 1 mol) was added dropwise over a period of
30 min at RT. HCl gas was evolved immediately. After
completing the addition of the H2SO4, the mixture was
shaken for 30 min; meanwhile, the residual HCl was ex-
hausted by suction. A white solid material was thus obtained
(108.5 g) (28).
3286, 3091, 1693, 1650, 1556, 1273, 1066, 753, 691. H
NMR (300 MHz, CDCl3, ppm) δ: 2.03 (s, 3H), 3.45 (dd, J =
6.0 and 16.9 Hz, 1H), 3.77 (dd, J = 5.2 and 16.9 Hz, 1H),
5.58 (dd, J = 5.6 and 13.1 Hz, 1H), 6.90 (d, J = 6.3 Hz,1H),
7.24-7.60 (m, 8H), 7.91 (d, J = 7.5 Hz, 2H). 13C NMR
(75 MHz, CDCl3, ppm) δ: 23.5, 43.3, 50.0, 126.6, 127.5,
128.2, 128.7, 128.8, 133.6, 136.7, 141.6, 169.6, 199.3.
The desired pure product(s) was characterized by compar-
ison of their physical data with those of known β-amido car-
bonyl compounds (10–26). The spectral data of some
representative β-amido ketones/esters are given as follows.
Typical experimental procedure for the one-pot
preparation of N-(3-oxo-1,3-diphenylpropyl) acetamide
(Table 2, entry 1)
N-(1,3-Diphenyl-3-oxo-propyl) benzamide
A solution of the benzaldehyde (1 mmol), acetophenone
(1 mmol), acetyl chloride (0.5 mL), and acetonitrile in the
presence of magnesium hydrogensulfate (20 mol%) was
stirred at RT for the appropriate time (Table 2). The progress
of the reaction was followed by TLC. After completion of
the reaction, the reaction mixture was filtered and the heter-
ogeneous catalyst was recovered. Then, the residue solution
was poured into 50 mL of ice water, the solid was separated
and recrystallized twice using ethyl acetate/petroleum ether,
which gave the desired pure N-(1,3-diphenyl-3-oxo-propyl)
acetamide in 89% yield (Table 2, entry 1). IR (KBr, cm–1):
Table 2, entry 2. IR (KBr, cm–1): 3306, 3062, 1681, 1634,
1
1599, 1488, 1357, 981, 754. H NMR (300 MHz, CDCl3,
ppm) δ: 3.52 (dd, J = 6.0 and 16.4 Hz, 1H), 3.87 (dd, J = 4.8
and 16.8 Hz, 1H), 5.73–5.78 (m, 1H), 7.22 (t, J = 7.2 Hz,
1H), 7.30 (t, J = 7.6 Hz, 2H) 7.37–7.45 (m, 5H), 7.49 (t, J =
7.2 Hz, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.60 (d, J = 8.0 Hz,
1H), 7.82 (d, J = 8.0 Hz, 2H), 7.90 (d, J = 8.0 Hz, 2H). 13C
NMR (75 MHz, CDCl3, ppm) δ: 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.
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379
Table 2 (continued).
1649, 1558, 1505, 1774,1296, 1226, 1047, 807, 754. 1H
NMR (500 MHz, CDCl3, ppm) δ: 2.00 (s, 3H), 3.46 (dd, J =
6.6 and 15.8 Hz, 1H), 3.56 (dd, J = 6.1 and 15.7 Hz, 1H),
3.73 (s, 3H), 3.85 (s, 3H), 5.69 (dd, J = 2.3 and 6.5 Hz, 1H),
6.73 (dd, J = 3.0 and 8.9 Hz, 1H), 6.79 (d, J = 8.9 Hz, 1H),
6.83 (d, J = 8.4 Hz, 1H), 6.87 (d, J = 3.0 Hz, 1H), 7.43 (t,
J = 7.6 Hz, 2H), 7.55 (t, J = 7.3 Hz, 1H), 7.92 (d, J =
7.4 Hz, 2H). 13C NMR (125 MHz, CDCl3, ppm) δ: 23.5,
43.0, 48.0, 55.7, 55.8, 111.7, 112.8, 115.0, 128.2, 128.6,
129.5, 133.2, 136.8, 150.8, 153.6, 169.0, 198.6. MS m/z (%):
327.2 (M+, 17), 285.2 (19), 284.2 (100), 237.1 (16), 208.1
(17), 180.2 (27), 166.1 (62), 151.1 (13), 136.1 (12), 105.1
(45), 77.2 (23), 43.2 (14). C19H21NO4 requires (%): C 69.71,
H 6.47, N 4.28; found: C 69.56, H 6.39, N 4.34.
N-[1-Phenyl-3-oxo-3-(4-methoxyphenyl)propyl]
acetamide
Table 2, entry 3. IR (KBr, cm–1): 3260, 1680, 1640, 1600,
1
1570, 1255, 1170, 990, 700. H NMR (300 MHz, CDCl3,
ppm) δ: 2.00 (s, 3H), 3.34 (dd, J = 5.9 and 16.6 Hz, 1H),
3.67 (dd, J = 5.3 and 16.6 Hz, 1H), 3.84 (s, 3H), 5.50–5.57
(m, 1H), 6.86 (s, 1H), 6.89 (d, J = 8.8 Hz, 2H), 7.18–7.34
(m, 5H), 7.88 (d, J = 8.8 Hz, 2H). 13C NMR (75 MHz,
CDCl3, ppm) δ: 23.4, 42.8, 50.0, 55.5, 113.8, 126.4, 127.3,
128.5, 129.7, 130.4, 141.1, 163.8, 169.5, 197.1.
N-[1-(2,5-Dimethoxyphenyl)-3-oxo-3-phenylpropyl]
acetamide
Table 2, entry 17. IR (KBr, cm–1): 3296, 3086, 1689,
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Can. J. Chem. Vol. 86, 2008
Table 2 (concluded).
aYields refer to the isolated pure products. All known products have been reported previously inthe
literature and were characterized by comparison of mp, IR, and NMR spectra with authentic samples
(10–26).
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Shaterian et al.
381
Table 3. Preparation of β-acetamido ketoesters in the presence of Mg(HSO4)2 as a catalyst at
room temperature.
aYields refer to the isolated pure products.
bRatio obtained from 1H NMR of the crude reaction mixture. All syn and anti diastereomers havebeen re-
ported previously in the literature, thus we compared 1H NMR spectra with authenticsamples (10–12, 26).
N-[1-(2,3-Dimethoxyphenyl)-3-oxo-3-(4-
methylphenyl)propyl] acetamide
Table 2, entry 18. IR (KBr, cm–1): 3301, 3081, 2941, 1686,
1651, 1610, 1552, 1503, 1466,1372, 1284, 1225, 1047, 807,
714. H NMR (500 MHz, CDCl3, ppm) δ: 1.99 (s, 3H), 2.38
Table 4. Recyclability of Mg(HSO4)2 in
the synthesis of N-(1,3-diphenyl-3-oxo-
propyl) acetamide.
1
(s, 3H), 3.42 (dd, J = 6.4 and 15.6 Hz, 1H), 3.51 (dd, J = 6.2
and 15.6 Hz, 1H), 3.72 (s, 3H), 3.84 (s, 3H), 5.68 (dd, J = 6.4
and 14.8 Hz, 1H), 6.72 (dd, J = 2.8 and 8.8 Hz, 1H), 6.78 (d,
J = 8.8 Hz, 1H), 6.87–6.86 (m, 2H), 7.22 (d, J = 7.9 Hz, 2H),
7.82 (d, J = 8.0 Hz, 2H). 13C NMR (125 MHz, CDCl3, ppm)
δ: 21.6, 23.4, 42.9, 47.9, 55.7, 55.8, 111.7, 112.7, 114.9,
128.3, 129.3, 129.7, 134.3, 144.0, 150.7, 153.6, 169.1, 198.2.
MS m/z (%): 341.2 (M+, 19), 299.2 (21), 298.2 (100), 251.2
(23), 208.1 (20), 180.2 (30), 166.1 (70), 151.1 (15), 136.1
(13), 119.1 (65), 105.1 (14), 91.2 (27), 77.2 (12), 43.2 (20).
C20H23NO4 requires (%): C 70.36, H 6.79, N 4.10; found: C
70.32, H 6.71, N 4.07.
Run no.
Yield (%)
1
2
3
4
5
89
87
88
85
84
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Can. J. Chem. Vol. 86, 2008
Table 5. Comparison result of magnesium hydrogensulfate with BiOCl (14), ZrOCl2·8H2O (15),
CeCl3 7H2O (21), ZnO (22), and I2 (23) in the synthesis of β-acetamido ketones.
J = 8.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H), 7.46 (t, J =
7.7 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.91 (d, J = 7.7 Hz,
2H). 13C NMR (125 MHz, DMSO-d6, ppm) δ: 20.8, 22.6,
44.5, 48.4, 121.5, 127.7, 128.0, 128.7, 133.2, 136.5, 140.5,
149.2, 168.3, 169.2, 197.0. MS m/z (%): 352.2 (M+, 8),
326.2 (2), 282.2 (100), 240.2 (41), 242.2(19), 178.2 (20),
167.1 (26), 149.1 (62), 136.2 (37), 122.2 (55), 105.2 (86),
77.2 (40), 57.2 (16), 43.2 (41). C19H19NO4 requires (%): C
70.14, H 5.89, N 4.31; found: C 70.08, H 5.78, N 4.24.
N-[1-(4-Acethoxy-2-methoxyphenyl)-3-oxo-3-
phenylpropyl] acetamide
Table 2, entry 19. IR (KBr, cm–1): 3281, 3096, 1768, 1686,
1653, 1602, 1558, 1511, 1366, 1304, 1279, 1199, 1029, 909,
1
741. H NMR (500 MHz, CDCl3, ppm) δ: 1.98 (s, 3H), 2.28
(s, 3H), 3.42 (dd, J = 6.3 and 16.8 Hz, 1H), 3.69 (dd, J = 5.4
and 16.8 Hz, 1H), 3.78 (s, 3H), 5.53 (dd, J = 5.9 and 13.8 Hz,
1H), 6.75 (d, J = 8.0 Hz, 1H), 6.87–6.97 (m, 3H), 7.45 (t, J =
7.6 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.90 (d, J = 8.5 Hz,
2H). 13C NMR (125 MHz, CDCl3, ppm) δ: 20.6, 23.3, 43.2,
49.9, 55.9, 115.5, 118.5, 122.8, 128.1, 128.7, 133.5, 136.6,
139.0, 140.0, 151.1, 169.0, 169.5, 198.4. MS m/z (%): 355.2
(M+, 15), 313.2 (28), 312.2 (57), 271.2 (20), 270.2 (100),
254.2 (19), 208.2 (10), 194.2 (24), 166.2 (35), 152.2 (49),
105.2 (82), 77.2 (31), 43.2 (22). C20H21NO5 requires (%): C
67.59, H 5.96, N 3.94; found: C 67.43, H 5.94, N 3.90.
N-[1-(3-Nitrophenyl)-3-oxo-3-(4-methylphenyl)propyl]
acetamide
Table 2, entry 21. IR (KBr, cm–1): 3301, 3069, 1680,
1645, 1606, 1531, 1352, 1202, 1180, 810, 741, 696. 1H
NMR (300 MHz, DMSO-d6, ppm) δ: 1.97 (s, 3H), 2.36 (s,
3H), 3.43 (dd, J = 5.5 and 17.4 Hz, 1H), 3.61 (dd, J = 8.3
and 17.4 Hz, 1H), 5.45 (dd, J = 7.6 and 13.4 Hz, 1H), 7.31
(d, J = 7.9 Hz, 2H), 7.62 (t, J = 7.9 Hz, 1H), 7.86–7.75 (m,
3H), 8.08 (d, J = 8.0 Hz, 1H), 8.22 (s, 1H), 8.49 (d, J =
7.5 Hz, 1H). 13C NMR (75 MHz, DMSO-d6) δ: 20.7, 22.6,
44.0, 48.5, 121.3, 121.8, 128.1, 129.1, 129.7, 133.7, 133.9,
143.7, 145.6, 147.8, 168.6, 196.1. MS m/z (%): 326.3 (M+,
0.8), 283.2 (20), 267.2 (12), 189.2 (24), 190.2 (17), 165.2
(38), 151.2 (33), 134.2 (13),119.2 (100), 105.2 (12), 91.2
N-[1-(4-Acethoxyphenyl)-3-oxo-3-phenylpropyl] acetamide
Table 2, Entry 20. IR (KBr, cm–1): 3262, 3085, 2928,
1762, 1699, 1652, 1651, 1509, 1448, 1411, 1365, 1294,
1
1216, 1200, 911, 759, 691. H NMR (500 MHz, CDCl3,
ppm) δ: 2.01 (s, 3H), 2.28 (s, 3H), 3.44 (dd, J = 6.1 and
17.0 Hz, 1H), 3.73 (dd, J = 5.2 and 17.0 Hz, 1H), 5.56 (dd,
J = 5.8 and 13.6 Hz, 1H), 6.73 (d, J = 8.0 Hz, 1H), 7.03 (d,
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(43), 77.2 (6), 65.2 (14), 43.2 (26). C18H18N2O4 requires (%):
C 66.25, H 5.56, N 8.58; found: C 66.23, H 5.56, N 8.51.
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N-[1-(4-Methylphenyl)-3-oxo-3-(4-methylphenyl)propyl]
acetamide
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Table 2, entry 22. IR (KBr, cm–1): 3258, 3069, 1607,
1638, 1605, 1541, 1410, 1326, 1266, 1183, 998, 810, 722.
1H NMR (300 MHz, DMSO-d6, ppm) δ: 1.77 (s, 3H), 2.24
(s, 3H), 2.36 (s, 3H), 3.31 (dd, J = 6.1 and 15.9 Hz, 1H),
3.46 (dd, J = 8.0 and 16.7 Hz, 1H), 5.31 (dd, J = 7.7 and
14.2 Hz, 1H), 7.10 (d, J = 7.9 Hz, 2H), 7.21 (d, J = 8.0 Hz,
2H), 7.31 (d, J = 8.0 Hz, 2H), 7.83 (d, J = 8.1 Hz, 2H), 8.25
(d, J = 8.0 Hz, 1H). 13C NMR (75 MHz, DMSO-d6, ppm) δ:
20.6, 21.1, 22.6, 44.5, 48.8, 126.5, 128.1, 128.7, 129.2,
134.1, 135.8, 140.0, 143.5, 168.2, 196.7. MS m/z (%): 295.2
(M+, 12), 252.2 (100), 253.2 (21), 221.2 (13), 162.2 (10),
134.2 (49), 120.2 (70), 119.2 (91), 91.2 (44), 65.2 (14), 43.2
(14). C19H21NO2 requires (%): C 77.26, H 7.17, N 4.74;
found: C 77.20, H 7.13, N 4.70.
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(R)-Methyl 2-((S)-acetamido(phenyl)methyl)-3-
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Table 3, entry 1 (mixture of diastereomers), data for the
1
major isomer. H NMR (500 MHz, CDCl3, ppm) δ: 1.97 (s,
3H), 2.11 (s, 3H), 3.71 (s, 3H), 4.07 (d, J = 5.5 Hz, 1H),
5.72 (dd, J = 5.5 and 9.0 Hz, 1H), 6.91 (d, J = 8.1 Hz, 1H),
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(R)-Methyl 2-((S)-acetamido(4-chlorophenyl)methyl)-3-
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1
major isomer. H NMR (500 MHz, CDCl3, ppm) δ: 1.98 (s,
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3H), 2.13 (s, 3H), 3.73 (s, 3H), 4.07 (d, J = 5.5 Hz, 1H),
5.69 (dd, J = 5.5 and 9.0 Hz, 1H), 6.93 (d, J = 8.3 Hz, 1H),
7.20 (d, J = 8.8 Hz, 2H), 7.26(d, J = 7.9 Hz, 2H).
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Catal. A: Chem. 242, 129 (2005).
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Table 3, entry 4 (mixture of diastereomers), data for the
1
major isomer. H NMR (500 MHz, CDCl3, ppm) δ: 1.20 (t,
J = 7.1 Hz, 3H), 1.99 (s, 3H), 2.16 (s, 3H), 4.01 (d, J =
5.9 Hz, 1H), 4.15 (q, J = 7.0 Hz, 2H), 5.76 (dd, J = 6.2 and
8.9 Hz, 1H), 6.99 (d, J = 8.8 Hz, 1H), 7.24–7.33 (m, 5H).
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N-((1S,2R)-2-Methyl-3-oxo-1,3-diphenylpropyl)acetamide
Table 3, entry 6 (mixture of diastereomers), data for the ma-
1
jor isomer. H NMR (500 MHz, CDCl3, ppm) δ: 1.32 (d, J =
7.2 Hz, 3H), 2.04 (s, 3H), 4.03–4.13 (m, 1H), 5.35 (dd, J = 4.5
and 8.9 Hz, 1H), 6.99–7.27 (m, 9H), 7.79 (d, J = 7.4 Hz, 2H).
26. B. Das, K.R. Reddy, Y. Srinivas, and R.A. Kumar. Can. J.
Acknowledgments
Chem. 85, 479 (2007).
27. F. Shirini, M.A. Zolfigol, and B. Mallakpour. Russ. J. Org.
Chem. 41, 625 (2005).
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Hajipour, and I.M. Baltork. Tetrahedron Lett. 43, 1555 (2002).
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We are thankful to the Sistan and Baluchestan University
Research Council for partial support of this work.
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© 2008 NRC Canada