Solvent-free, microwave-assisted, one-pot synthesis of 2-acetyl-n,3-diaryl- 4-nitro-butanamides

Article abstract of DOI:10.1080/00397911003707113

A microwave-assisted diastereoselective synthesis of 2-acetyl-N,3-diaryl-4- nitro-butanamides via reaction of anilines, 2,2,6-trimethyl-4H-1,3-dioxin-4-one, and -nitrostyrenes in the presence of catalytic amounts of triethylamine under solvent-free conditions is described.

Full text of DOI:10.1080/00397911003707113

This article was downloaded by: [University of Washington Libraries]
On: 05 November 2014, At: 20:43
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Solvent-Free, Microwave-Assisted, One-
Pot Synthesis of 2-Acetyl-N,3-diaryl-4-
nitro-butanamides
Issa Yavari a , Saeideh Beheshti a , Zinatossadat Hossaini a & Sanaz
Souri a
a Chemistry Department , Tarbiat Modares University , Tehran , Iran
Published online: 25 Feb 2011.
To cite this article: Issa Yavari , Saeideh Beheshti , Zinatossadat Hossaini & Sanaz Souri (2011)
Solvent-Free, Microwave-Assisted, One-Pot Synthesis of 2-Acetyl-N,3-diaryl-4-nitro-butanamides,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 41:6, 907-913, DOI: 10.1080/00397911003707113
To link to this article: http://dx.doi.org/10.1080/00397911003707113
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 41: 907–913, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003707113
SOLVENT-FREE, MICROWAVE-ASSISTED, ONE-POT
SYNTHESIS OF 2-ACETYL-N,3-DIARYL-4-NITRO-
BUTANAMIDES
Issa Yavari, Saeideh Beheshti, Zinatossadat Hossaini, and
Sanaz Souri
Chemistry Department, Tarbiat Modares University, Tehran, Iran
GRAPHICAL ABSTRACT
Abstract A microwave-assisted diastereoselective synthesis of 2-acetyl-N,3-diaryl-4-nitro-
butanamides via reaction of anilines, 2,2,6-trimethyl-4H-1,3-dioxin-4-one, and b-nitrostyr-
enes in the presence of catalytic amounts of triethylamine under solvent-free conditions is
described.
Keywords Aniline; butanamide; Michael addition; microwave irradiation; b-nitrostyrene
INTRODUCTION
Michael addition of carbon nucleophiles to electron-deficient olefins is a classi-
cal and fundamental carbon–carbon bond-forming reaction. Michael adducts are
versatile building blocks for agricultural and pharmaceutical compounds.[1] This
reaction and its close variants have been extensively used in organic synthesis.[2]
Generally, Michael additions are conducted in a suitable solvent in the presence of
a strong base, either at room temperature or at elevated temperatures.[3] Because
of the presence of the strong base, side reactions such as multiple condensations,
polymerizations, rearrangements, and retro-Michael additions are common. These
undesirable side reactions decrease the yield of the target adduct and render its
purification difficult.
b-Nitrostyrenes, because of their strongly electron-withdrawing group,[4]
can be easily transformed into a variety of valuable functionalities such as amines,
Received October 12, 2009.
Address correspondence to Issa Yavari, Chemistry Department, Tarbiat Modares University, P.O.
Box 14115-175, Tehran, Iran. E-mail: yavarisa@modares.ac.ir
907

908
I. YAVARI ET AL.
Scheme 1. Synthesis of 2-acetyl-N,3-diaryl-4-nitro-butanamides.
ketoximes, hydroxylamines, and nitroalkanes.[5–8] Therefore, conjugate addition to
b-nitrostyrenes has received much attention in recent years. There have been many
reports on the conjugate addition of b-nitrostyrenes mediated by organometallics
including Grignard reagents,[9,10] alkyllithiums, and organoaluminums. However,
most of these reagents were not satisfactory because of undesirable side reactions
and poor conversion. For the purposes of ecofriendly ‘‘green chemistry,’’ a reaction
should ideally be conducted under solvent-free conditions with minimal or no
side-product formation and utmost atom economy.[11]
In this context, we planned to conduct the Michael addition reaction under
environmentally benign solvent-free conditions, wherein several disadvantages such
as long reaction time and tedious workup can be overcome. As part of our current
studies on the development of new routes in organic synthesis,[12–15] we report an
efficient synthesis of functionalized 2-acetyl-N,3-diaryl-4-nitro-butanamides
(Scheme 1).
RESULTS AND DISCUSSION
The reaction of anilines (1) and 2,2,6-trimethyl-4H-1,3-dioxin-4-one (2) with
b-nitrostyrenes (3) in the presence of catalytic amounts of Et3N with microwave
irradiation under solvent-free conditions led to 2-acetyl-N,3-diaryl-4-nitro-butana-
mides (4) in good yields (Scheme 1). Structures of compounds 4a–j were assigned
by infrared (IR), 1H NMR, and 13C NMR spectra. For example, the 1H NMR spec-
trum of 4a exhibited characteristic signals for the methyl and aryl protons at appro-
priate reagions of the spectrum. Because of the presence of a stereogenic center in
these products, protons of the CH2 group are diasterotopic and exhibit (AB)X
systems. The adjacent methine groups in 4a appear as a multiplet (4.31–4.42 ppm)
and doublet (4.65 ppm). The 13C NMR spectrum of 4a showed the carbonyl groups
at 166.0 and 201.9 ppm. The mass spectrum of 4a displayed a molecular ion peak at
m=z ¼ 395. Compounds 4a-j possess two stereogenic centers, and they can exist as

2-ACETYL-N,3-DIARYL-4-NITRO-BUTANAMIDES
909
Scheme 2. Rationalization for the formation of 2-acetyl-N,3-diaryl-4-nitro-butanamides.
two diastereoisomers. The 1H and 13C NMR spectra of these compounds confirm the
presence of these diastereoisomers.
Although the mechanistic details of the reaction are not known, a plausible
rationalization may be advanced to explain the product formation. Presumably,
the intermediate 5 formed from the reaction of 1 and 2 is converted to 6 in the pres-
ence of Et3N. Finally, Michael addition of 6 to b-nitrostyrene 3 leads to the desired
products 4 (Scheme 2).
In conclusion, microwave irradiation of anilines, 2,2,6-trimethyl-4H-
1,3-dioxin-4-one, and b-nitrostyrenes in the presence of a catalytic amount of
Et3N, under solvent-free conditions, led to 2-acetyl-N,3-diaryl-4-nitro-butanamides
in good yields. The present procedure has the advantages that the Michael addition
reaction is carried out under environmentally benign solvent-free conditions and the
starting materials can be used without prior activation or modification.
EXPERIMENTAL
Anilines (1), 2,2,6-trimethyl-4H-1,3-dioxin-4-one (2), and Et3N were obtained
from Fluka and were used without further purification. b-Nitrostyrenes (3) were pre-
pared according to the literature procedure.[16] Melting points were determined on an
Electrothermal-9100 apparatus. IR spectra were measured with a Shimadzu IR-460
spectrometer. 1H and 13C NMR spectra were found with a Bruker DRX-500 Avance
instrument in acetone-d6 at 500 and 125.7 MHz, respectively (d in parts per million, J
in hertz). Electron-impact mass spectrometry (70 eV) was conducted on Finnigan-
MAT-8430 mass spectrometer, in m=z. Elemental analyses (C, H, N) were performed
with a Vario EL III CHNOS elemental analyzer. The reactions were carried out in a
domestic microwave oven, MW 3070 GS, (Feller, Germany).
General Procedure
Anilines (1, 2 mmol) and 2,2,6-trimethyl-4H-1,3-dioxin-4-one (2, 0.28 g,
2 mmol) were mixed in an agate mortar for 2 min and then irradiated in the micro-
wave oven at 900 W for 3 min. A mixture of Et3N (0.08 g) and b-nitrostyrene
(3, 2 mmol) was added to the reaction mixture and irradiated in the microwave oven.
After completion of the reaction (6 min), as indicated by thin-layer chromatography
(TLC, hexane=AcOEt 4:1), the workup of the reaction is simply done by extraction
with acetone and evaporating the solvent under reduced pressure to leave a residue,
which was purified by column chromatography (SiO2; hexane=AcOEt 5:1) to afford
the pure desired products.

910
I. YAVARI ET AL.
Selected Data
2-Acetyl-N-(2,4-dichlorophenyl)-4-nitro-3-phenyl-butanamide (4a). Yellow
oil, yield: 0.71 g (90%). IR (KBr) (nmax=cmꢀ1): 3450, 3265, 1719, 1655, 1551, 1513,
1
1473, 1377, 1293, 1117, 816, 695. H NMR (500 MHz, acetone-d6): d ¼ 2.08 (3 H,
2
s, Me), 4.31–4.42 (1 H, m, CH), 4.65–4.82 (1 H, d, J 10.8 Hz, CH), 4.88–5.11
(2 H, m, CH2), 7.22–7.55 (8 H, m, CH), 9.21 (1 H, s, NH). 13C NMR
(125.7 MHz, acetone-d6): d ¼ 29.6 (Me), 47.6 (CH), 63.9 (CH), 78.7 (CH2), 126.8
(CH), 127.9 (CH), 128.7 (CH), 129.4 (CH), 129.6 (CH), 129.8 (CH), 129.9 (C),
=
=
131.2 (C), 134.1 (C), 138.0 (C), 166.0 (C O), 201.9 (C O). EI-MS: 395 (Mþ, 2),
246 (16), 162 (100), 77 (62), 43 (49). Anal. calcd. (%) for C18H16Cl2N2O4 (395.23):
C, 54.70; H, 4.08; N, 7.09. Found: C, 54.65; H, 3.98; N, 7.00.
2-Acetyl-4-nitro-N,3-diphenyl-butanamide (4b). White powder, yield:
0.60 g (92%), mp 168–170 ꢁC. IR (KBr) (nmax=cmꢀ1): 3275, 1715, 1651, 1552, 1440,
1377, 1354, 1152, 751, 694. 1H NMR (500 MHz, acetone-d6): d ¼ 2.34 (3 H, s,
3
Me), 4.33–4.35 (2 H, m, CH), 4.83–4.94 (2 H, m, CH), 7.03 (1 H, t, J 7.3 Hz,
3
CH), 7.18 (1 H, t, J 7.3 Hz, CH), 7.20 (2 H, t, J 7.5 Hz, CH), 7.26 (2 H, t, J
3
3
3
3
7.4 Hz, CH), 7.35 (2 H, d, J 7.5 Hz, CH), 7.38 (2 H, d, J 7.1 Hz, CH), 9.35 (1 H,
s, NH). 13C NMR (125.7 MHz, acetone-d6): d ¼ 29.8 (CH), 43.9 (Me), 64.9 (CH),
79.1 (CH2), 120.8 (CH), 125.0 (CH), 128.5 (CH), 129.3 (CH), 129.3 (CH), 129.4
=
(CH), 138.4 (C), 139.1 (C), 165.3 (CONH2), 202.2 (C O). EI-MS: 326 (Mþ, 1),
238 (4), 177 (15), 93 (100), 77 (60), 43 (50). Anal. calcd. (%) for C18H18N2O4
(326.34): C, 66.25; H, 5.56; N, 8.58. Found: C, 66.10; H, 5.54; N, 8.35.
2-Acetyl-N-(4-methoxyphenyl)-4-nitro-3-phenyl-butanamide (4c). Yellow
powder, mp 170–172 ꢁC. IR (KBr) (nmax=cmꢀ1): 3280, 1711, 1642, 1551, 1508, 1413,
1375, 1249, 1028, 824, 697. EI-MS: 356 (Mþ, 1), 207 (17), 123 (100), 77 (59), 43 (52).
Anal. calcd. (%) for C19H20N2O6 (356.37): C, 64.04; H, 5.66: N, 7.86. Found: C,
1
63.95; H, 5.60; N, 7.94. NMR data for the major isomer (0.47 g, 66%); H NMR
3
(500 MHz, acetone-d6): d ¼ 2.12 (3 H, s, Me), 3.71 (3 H, s, MeO), 4.19 (1 H, d, J
3
8.9 Hz, CH), 4.28–4.36 (1 H, m, CH), 4.83–5.01 (2 H, m, CH2), 6.76 (2 H, d, J
3
3
9.0 Hz, CH), 7.21 (2 H, d, J 7.0 Hz, CH), 7.26 (2 H, t, J 7.7 Hz, CH), 7.34–7.38
(1 H, m, CH), 7.35 (2 H, d, 3J 9.1 Hz, CH), 9.28 (1 H, s, NH). 13C NMR
(125.7 MHz, acetone-d6): d ¼ 29.7 (Me), 43.9 (CH), 55.6 (MeO), 64.7 (CH), 79.2
(CH2), 114.5 (CH), 122.5 (CH), 128.4 (CH), 129.2 (C), 129.3 (CH), 132.1 (C),
=
138.5 (C), 157.4 (C), 165.0 (CONH2), 202.3 (C O). NMR data for the minor isomer
1
(0.24 g, 34%): H-NMR (500 MHz, acetone-d6): d ¼ 2.06 (1 H, s, Me), 3.78 (1 H, s,
3
MeO), 4.28–4.36 (2 H, m, CH), 4.83–5.01 (2 H, m, CH2), 6.90 (2 H, d, J 9.0 Hz,
CH), 7.18 (2 H, d, 3J 7.4 Hz, CH), 7.25–7.28 (1 H, m, CH), 7.32 (2 H, t, 3J
7.6 Hz, CH), 7.54 (1 H, d, 3J 9.0 Hz, CH), 9.50 (1 H, s, NH). 13C NMR
(125.7 MHz, acetone-d6): d ¼ 29.9 (Me), 43.9 (CH), 55.7 (MeO), 64.8 (CH), 78.8
(CH2), 114.7 (CH), 122.4 (CH), 128.6 (CH), 129.1 (C), 129.5 (CH), 132.4 (C),
=
138.8 (C), 157.6 (C), 165.5 (CONH2), 201.6 (C O).
2-Acetyl-N-(2-cyanophenyl)-4-nitro-3-phenyl-butanamide (4d). White
powder, mp 159–161 ꢁC. IR (KBr) (nmax=cmꢀ1): 3410, 2250, 1717, 1694, 1577,
1543, 1518, 1442, 1373, 762. EI-MS: 351 (Mþ, 1), 202 (18), 118 (100), 77 (64),
43 (55). Anal. calcd. (%) for C19H17N3O4(351.35): C, 64.95; H, 4.88; N, 11.96.

2-ACETYL-N,3-DIARYL-4-NITRO-BUTANAMIDES
911
Found: C, 64.82; H, 4.80; N, 12.07. NMR data for the major isomer (0.39 g, 56%):
3
1H NMR (500 MHz, CDCl3): d ¼ 1.99 (3 H, s, Me), 4.13 (1 H, d, J 10.9 Hz, CH),
4.27–4.31 (1 H, m, CH), 4.82–5.32 (2 H, m, CH2), 7.19 (1 H, t, 3J 7.6 Hz,
CH), 7.22 (1 H, d, 3J 7.0 Hz, CH), 7.28–7.33 (4 H, m, CH), 7.51 (1 H, t, 3J
3
8.3 Hz), 7.52–7.87 (1 H, m, CH), 7.86 (1 H, d, J 8.4 Hz, CH), 8.61 (1 H, s, NH).
13C NMR (125.7 MHz, CDCl3): d ¼ 30.2 (Me), 43.9 (CH), 62.8 (CH), 78.0 (CH2),
115.7 (CN), 124.6 (C), 127.8 (CH), 128.5 (CH), 128.8 (CH), 129.1 (CH), 129.3
(CH), 132.4 (CH), 133.6 (C), 133.9 (CH), 135.0 (C), 164.6 (CONH2), 203.9
1
(C O). NMR data for the minor isomer (0.31 g, 44%): H NMR (500 MHz, CDCl3):
=
d ¼ 2.47 (3 H, s, Me), 4.21 (1 H, d, 3J 8.4 Hz, CH), 4.27–4.31 (1 H, m, CH), 4.82–5.32
(2 H, m, CH2), 7.21 (1 H, d, 3J 7.0 Hz, CH), 7.28–7.39 (5 H, m, CH), 7.55 (1 H, d, 3J
7.7 Hz), 7.52–7.87 (1 H, m, CH), 8.15 (1 H, d,3J 8.2 Hz, CH), 8.93 (1 H, s, NH). 13
C
NMR (125.7 MHz, CDCl3): d ¼ 31.0 (Me), 45.3 (CH), 64.4 (CH), 78.6 (CH2), 115.9
(CN), 124.7 (C), 127.9 (CH), 128.5 (CH), 128.9 (CH), 129.2 (CH), 129.5 (CH), 132.7
=
(CH), 133.8 (C), 134.0 (CH), 135.6 (C), 164.9 (CONH2), 204.7 (C O).
2-Acetyl-4-nitro-N-(2-nitrophenyl)-3-phenyl-butanamide
(4e). Yellow
powder, mp 90–92 ꢁC. IR (KBr) (nmax=cmꢀ1): 3345, 1723, 1653, 1665, 1550, 1498,
1451, 1340, 1274, 1150, 734, 698. EI-MS: 571 (Mþ, 2), 222 (14), 138 (100), 77 (60),
43 (55). Anal. calcd. (%) for C18H17N3O6 (571.34): C, 58.22; H, 4.61; N, 11.32. Found:
C, 58.12; H, 4.52; N, 11.13. NMR data for the major isomer (0.47 g, 63%): 1H NMR
(500 MHz, CDCl3): d ¼ 2.45 (3 H, s, Me), 4.19 (1 H, d, 2J 9.9 Hz, CH), 4.30 (1 H, m,
CH), 4.83 (2 H, m, CH2), 7.18–7.38 (6 H, m, CH), 7.58 (1 H, t, 3J 7.6 Hz, CH), 8.13
(1 H, d, 3J 8.4 Hz, CH), 8.32 (1 H, d, 3J 8.4 Hz, CH), 10.41 (1 H, s, NH). 13C NMR
(125.7 MHz, CDCl3): d ¼ 29.6 (Me), 43.6 (CH), 65.1 (CH), 77.7 (CH2), 122.5 (CH),
124.5 (CH), 125.9 (CH), 128.7 (CH), 129.4 (CH), 133.3 (C), 135.6 (C), 135.8 (C),
1
164.8 (CONH2), 202.2 (C O). NMR data for the minor isomer (0.28 g, 37%); H
=
NMR (500 MHz, CDCl3: d ¼ 2.059 (3 H, s, Me), 4.11 (1 H, d, 2J 10.4 Hz, CH), 4.30
3
(1 H, m, CH), 4.83 (2 H, m, CH2), 7.18–7.38 (6 H, m, CH), 7.7 (1 H, t, J 7.6 Hz,
3
3
CH), 8.25 (1 H, d, J 8.4 Hz, CH), 8.67 (1 H, d, J 8.4 Hz, CH), 10.82 (1 H, s, NH).
13C NMR (125.7 MHz, CDCl3): d ¼ 30.2 (Me), 44.2 (CH), 65.7 (CH), 77.0 (CH2),
122.4 (CH), 124.2 (CH), 125.6 (CH), 128.5 (CH), 129.2 (CH), 133.1 (C), 135.4 (C),
=
135.8 (C), 165.2 (CONH2), 202.2 (C O).
2-Acetyl-4-nitro-N-phenyl-3-p-tolyl-butanamide (4f). White powder,
yield: 0.61 g (89%), mp 193–195 ꢁC. IR (KBr) (nmax=cmꢀ1): 3270, 1712, 1649, 1555,
1
1440, 1354, 1153, 804, 750. H NMR (500 MHz, acetone-d6): d ¼ 2.21 (3 H, s, Me),
d ¼ 2.35 (3 H, s, Me), 4.29–4.35 (2 H, m, CH), 4.81–4.92 (2 H, m, CH), 7.03–7.09 (3
H, m, CH), 7.21–7.27 (4 H, m, CH), 7.39–7.40 (2 H, m, CH), 9.45 (1 H, s, NH).
13C NMR (125.7 MHz, acetone-d6): d ¼ 20.9 (Me), 29.7 (Me), 43.5 (CH), 64.9 (CH),
79.3 (CH2), 120.6 (CH), 120.7 (CH), 124.9 (CH), 129.1 (CH), 129.4 (CH), 129.9
=
(CH), 135.3 (C), 138.0 (C), 128.7 (CH), 139.2 (C), 165.3 (CONH2), 202.3 (C O).
EI-MS: 340 (Mþ, 2), 177 (18), 93 (100), 91 (63), 43 (52). Anal. calcd. (%) for
C19H20N2O4 (340.37): C, 67.05; H, 5.92; N, 8.23. Found: C, 67.00; H, 5.80; N, 8.32.
2-Acetyl-N-(4-methoxyphenyl)-4-nitro-3-p-tolyl-butanamide (4g). White
powder, yield: 0.69 g (93%), mp 176–178 ꢁC. IR (KBr) (nmax=cmꢀ1): 3275,
1715, 1649, 1554, 1511, 1433, 1377, 1354, 1251, 1038, 845. H NMR (500 MHz,
1

912
I. YAVARI ET AL.
acetone-d6): d ¼ 2.21 (3 H, s, Me), 2.34 (3 H, s, Me), 3.78 (3 H, s, MeO), 4.27–4.29 (2
3
3
H, m, CH), 4.80–4.90 (2 H, m, CH2), 6.77 (2 H, d, J 7.1 Hz, CH), 7.07 (2 H, d, J
7.9 Hz, CH), 7.23–7.26 (4 H, m, CH), 9.29 (1 H, s, NH). 13C NMR (125.7 MHz,
acetone-d6): d ¼ 20.9 (Me), 29.9 (CH), 43.5 (Me), 55.6 (MeO), 64.8 (CH), 79.3
(CH2), 114.5 (CH), 122.4 (CH), 129.0 (CH), 129.9 (CH), 132.3 (þC), 135.4 (C),
=
138.0 (C), 157.4 (C), 165.0 (CONH2), 202.4 (C O). EI-MS: 370 (M , 1), 207 (15),
123 (100), 91 (66), 43 (54). Anal. calcd. (%) for C20H22N2O5 (370.39): C, 64.85; H,
5.99; N, 7.56. Found: C, 64.51; H, 5.78; N, 7.67.
2-Acetyl-N-(2,4-dichlorophenyl)-4-nitro-3-p-tolyl-butanamide (4h). Yellow
powder, mp 146–148 ꢁC. IR (KBr) (nmax=cmꢀ1): 3240, 3095, 1722, 1651, 1554, 1526,
1472, 1377, 1297, 1149, 821, 545. EI-MS: 409 (Mþ, 1), 246 (18), 163 (100), 91 (62), 43
(53). Anal. calcd. (%) for C19H18Cl2N2O4(409.26): C, 55.76; H, 4.43; N, 6.84. Found:
1
C, 55.84; H, 4.49; N, 6.95. NMR data for the major isomer (0.72 g, 88%): H NMR
(500 MHz, CDCl3): d ¼ 1.94 (3 H, s, Me), 2.33 (3 H, s, Me), 4.02 (1 H, d, 3J 11.1 Hz,
CH), 4.16–4.20 (1 H, m, CH), 4.76–4.93 (2 H, m, CH2), 7.06 (2 H, d, 3J 7.9 Hz, CH),
7.12–7.16 (3 H, m, CH), 7.31 (1 H, d, 4J 2.25 Hz, CH), 7.94 (1 H, d, 3J 8.8 Hz, CH),
8.50 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): d ¼ 21.03 (Me), 29.3 (Me), 43.8
(CH), 63.1 (CH), 77.4 (CH2), 122.8 (CH), 124.4 (C), 127.6 (CH), 127.8 (CH),
128.8 (CH), 129.8 (CH), 130.0 (C), 131.7 (C), 132.4 (C), 138.6 (C), 164.1 (CONH2),
=
1
204.8 (C O). NMR data for the minor isomer (0.72 g, 88%); H NMR (500 MHz,
CDCl3): d ¼ 2.27 (3 H, s, Me), 2.41 (3 H, s, Me), 4.08 (1 H, d, 3J 8.0 Hz, CH), 4.16–
4.20 (1 H, m, CH), 4.75–4.93 (2 H, m, CH2), 7.07 (2 H, d, 3J 7.9 Hz, CH), 7.12–7.16
4
(2 H, m, CH), 7.25–7.27 (1 H, m, CH), 7.41 (1 H, d, J 2.25 Hz, CH), 8.19 (1 H, d,
3J 8.8 Hz, CH), 8.82 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): d ¼ 22.6 (Me),
29.7 (Me), 45.1 (CH), 64.7 (CH), 78.0 (CH2), 122.9 (CH), 124.7 (C), 127.7
(CH), 127.8 (CH), 129.1 (CH), 130.1 (CH), 130.4 (C), 132.4 (C), 132.5 (C), 138.7
=
(C), 164.4 (CONH2), 205.2 (C O).
2-Acetyl-3-(4-bromophenyl)-4-nitro-n-phenylbutanamide
(4i). White
powder, yield: 0.77 g (95%), mp 195–197 ꢁC. IR (KBr) (nmax=cmꢀ1): 3261, 3014,
1734, 1653, 1601, 1541, 1436, 1364, 1217, 1006, 752. H NMR (500 MHz, CDCl3):
1
d ¼ 2.03 (3 H, s, Me), 3.93–3.99 (1 H, m, CH), 4.18–4.23 (1 H, m, CH), 4.75–4.82
(2 H, m, CH2), 7.03–7.52 (9 H, m, CH), 8.07 (1 H, s, NH). 13C NMR
(125.7 MHz, CDCl3): d ¼ 30.7 (Me), 44.3 (CH), 64.7 (CH), 78.0 (CH2), 120.16 (C),
122.9 (CH), 125.4 (CH), 129.1 (CH), 129.5 (CH), 132.3 (CH), 134.9 (C), 137.0 (C),
þ
=
163.6 (CONH2), 202.6 (C O). EI-MS: 405 (M , 1), 177 (16), 93 (100), 77 (65), 43
(56). Anal. calcd. (%) for C18H17BrN2O4 (405.24): C, 53.35; H, 4.23; N, 6.91. Found:
C, 53.29; H, 4.28; N, 6.88.
2-Acetyl-3-(4-chlorophenyl)-4-nitro-n-phenylbutanamide
(4j). White
powder, yield: 0.69 g (96%), mp 189–191 ꢁC. IR (KBr) (nmax=cmꢀ1): 3263, 3014,
1
2356, 1734, 1604, 1547, 1437, 1364, 1216, 1094, 824. H NMR (500 MHz, CDCl3):
d ¼ 2.43 (3 H, s, Me), 3.95–4.01 (1 H, m, CH), 4.22 (1 H, d, 3J 7.4 Hz, CH),
4.78–4.92 (2 H, m, CH2), 7.13–7.53 (9 H, m, CH), 7.94 (1 H, s, NH). 13C NMR
(125.7 MHz, CDCl3): d ¼ 21.5 (Me), 30.3 (CH), 43.4 (CH), 63.1 (CH2), 120.1
(CH), 120.4 (CH), 125.3 (CH), 125.5 (CH), 129.1 (Cþ), 129.2 (C), 129.4 (C), 129.7
=
(C), 172.0 (CONH2), 203.2 (C O). EI-MS: 360 (M , 1), 177 (15), 93 (100), 77

2-ACETYL-N,3-DIARYL-4-NITRO-BUTANAMIDES
913
(66), 43 (54). Anal. calcd. (%) for C18H17ClN2O4 (360.79): C, 59.92; H, 4.75; N, 7.76.
Found: C, 59.78; H, 4.64; N, 7.70.
REFERENCES
1. Berner, O. M.; Tedeschi, L.; Enders, D. Asymmetric Michael additions to nitroalkenes.
Eur. J. Org. Chem. 2002, 12, 1877–1894.
2. List, B.; Pojarliev, P.; Martin, H. J. Efficient proline-catalyzed Michael additions of
unmodified ketones to nitro olefins. Org. Lett. 2001, 3, 2423–2425.
3. Huang, H. B.; Jacobsen, E. N. Highly enantioselective direct conjugate addition of
ketones to nitroalkenes promoted by a chiral primary amineꢀthiourea catalyst. J. Am.
Chem. Soc. 2006, 128, 7170–7171.
4. Lalonde, M. P.; Chen, Y. G.; Jacobsen, E. N. A chiral primary amine thiourea catalyst for
the highly enantioselective direct conjugate addition of a,a-disubstituted aldehydes to
nitroalkenes. Angew. Chem. Int. Ed. Engl. 2006, 45, 6366–6370.
5. Perekalin, V. V.; Lipina, E. S.; Berestovitskaya, V. M.; Efremov, D. A. Nitroalkenes:
Conjugated Nitro Compounds; John Wiley: Chichester, 1994; ch. 2, p. 53.
6. Feuer, H.; Nielsen, A. T. Nitro Compounds: Recent Advances in Synthesis and Chemistry;
VCH: Weinheim, 1990; ch. 1, p. 1.
7. Barrett, A. G. M. Heterosubstituted nitroalkenes in synthesis. Chem. Soc. Rev. 1991, 20,
95–127.
8. Kabalka, G. W.; Guindi, L. H. M.; Varma, R. S. Selected reductions of conjugated
nitroalkenes. Tetrahedron 1990, 46, 7443–7457.
9. Yao, C. F.; Chen, W. C.; Li, Y. M. Reactions of b-nitrostyrenes with Gragnard reagents.
Tetrahedron Lett. 1996, 37, 6339–6342.
10. Yao, C. F.; Kao, K. H.; Liu, J. T.; Chu, C. M.; Wang, Y. Generation of nitroalkanes,
hydroximoyl halides, and nitrile oxides from the reactions of b-nitrostyrenes with
Grignard or organolithium reagents. Tetrahedron 1998, 54, 791–822.
11. Kaupp, G. Organic solid-state reactions with 100% yield. Top. Curr. Chem. 2005, 254,
95–183.
12. Habibi, A.; Mousavifar, L.; Yazdanbakhsh, M. R.; Yavari, I. Synthesis of
1-(2,6-dimethylphenyl)-N-hydroxy-4,4-dialkyl-2,5-dioxo-N-aryl- 3-pyrrolidine-carboxamides
from reaction of 2,6-dimethylphenyl isocyanide, alkylidene Meldrum’s acids, and arylhy-
droxylamines. Synth. Commun. 2008, 38, 873–880.
13. Yavari, I.; Mirzaei, A.; Moradi, L.; Mokhtarporiani-Sanandaj, A. Efficient synthesis of
trialkyl (E)-3-{3-oxo-2–3,4-dihydro-2-(1H)-quinoxalinylidene}-prop-1-ene-1,2,3-tricarboxy-
lates. Synth. Commun. 2007, 37, 1195–1200.
14. Yavari, I.; Karimi, E.; Djahaniani, H. Isocyanide-based multicomponent synthesis of
functionalized 2,6-dioxohexahydropyrimidines in 1 M aqueous glucose. Synth. Commun.
2007, 37, 2593–2599.
15. Yavari, I.; Sabbaghan, M. Synthesis of functionalized pyrroles by reaction of 3,4-
diacetylhexane-2,5-dione with primary amines in water. Synth. Commun. 2007, 37,
1791–1800.
16. Worrall, D. E. Nitrostyrene. Org. Synth. 1941, 1, 413.