One-pot reactions of nitroenamines with anilines and ethyl glyoxylate

Article abstract of DOI:10.1016/j.tet.2014.04.096

In a simple, one-pot, catalyst-free procedure starting from heterocyclic nitroenamines, substituted anilines and ethyl glyoxylate new ethyl 2-arylamino-3-nitro-propionates were prepared in good to excellent yields. Depending on the substituent pattern of the anilines applied, two routes for the one-pot reaction are suggested. Additionally, it was demonstrated that these multifunctional compounds of aza-Morita-Baylis-Hillman type were also formed in two-step protocols either from imines and nitroenamines or from the adducts of nitroenamines and ethyl glyoxylate with anilines.

Full text of DOI:10.1016/j.tet.2014.04.096

Tetrahedron xxx (2014) 1e6
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
One-pot reactions of nitroenamines with anilines and ethyl
glyoxylate
a
a
a
a
b
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Mihaly V. Pilipecz , Pal Scheiber , Zoltan Vincze , Tamas R. Varga , Gabor Toth ,
a,
*
ꢀ
Peter Nemes
a
ꢀ
Department of Chemistry, Faculty of Veterinary Science, Szent Istvan University, H-1400 Budapest, P.O. Box 2, Hungary
Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, H-1111 Budapest, Szt. Gellert ter 4, Hungary
b
ꢀ
ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
In a simple, one-pot, catalyst-free procedure starting from heterocyclic nitroenamines, substituted ani-
lines and ethyl glyoxylate new ethyl 2-arylamino-3-nitro-propionates were prepared in good to excellent
yields. Depending on the substituent pattern of the anilines applied, two routes for the one-pot reaction
are suggested. Additionally, it was demonstrated that these multifunctional compounds of aza-Mor-
itaeBayliseHillman type were also formed in two-step protocols either from imines and nitroenamines
or from the adducts of nitroenamines and ethyl glyoxylate with anilines.
Received 25 February 2014
Received in revised form 15 April 2014
Accepted 29 April 2014
Available online xxx
Keywords:
Nitroenamines
Imines
Ó 2014 Elsevier Ltd. All rights reserved.
One-pot reaction
Multifunctional compounds
HPLC monitoring
1. Introduction
These results demonstrating the strong nucleophilic character of
the b-carbon in pushepull alkenes prompted us to investigate the
Pushepull enamines, enamines with an electron withdrawing
group in the
applicability of these reactive nitroenamines (e.g., 1a) in similar
reactions with imines, envisaging the formation of multifunctional
adducts of aza-MBH type.
The aza-MoritaeBayliseHillman (aza-MBH) reaction, particu-
larly in the last decades, has become a very efficient, atom-
economic and attractive method with enormous utility and syn-
thetic potential.5 The reaction takes place between an activated
alkene and an imine in an additioneelimination sequence resulting
b-position, such as b b-enami-
-enaminonitriles,1
noesters,2 or nitroenamines3 proved to be valuable starting mate-
rials in the synthesis of various N-heterocycles in a number of cases.
In one of our previous work we reported the reactions of 1-
nitromethylenepyrrolidine (1a) with dicarbonyls.4 Using methyl
or phenyl glyoxal, glyoxylic acid and ethyl glyoxylate, the reaction
took place smoothly at room temperature without catalyst to give
the adducts 2 (Scheme 1). The reaction times were different, 12 h
and 2 h for methyl and phenyl glyoxal, respectively, but only 10 min
for glyoxylic acid and its ethyl ester.
in a-methylene-b-amino-carbonyl derivatives (Scheme 2).
Scheme 2. Formation of the aza-MBH adduct.
Many types of imines bearing different activating groups, such
as sulfonylimines, in particular tosylimines6 and also aryliminoa-
cetates7 have been developed and employed in the aza-MBH re-
action with various activated olefins leading to the formation of
densely functionalized valuable products that can be further ap-
plied in synthesis of a wide variety of compounds, useful in
chemistry of natural products, plant protection and particularly in
medicine and pharmaceutical industry. On the other hand, the
Scheme 1. The reactions of nitroenamine with glyoxylates.
* Corresponding author. E-mail address: Nemes.Peter@aotk.szie.hu (P. Nemes).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.04.096
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2
M.V. Pilipecz et al. / Tetrahedron xxx (2014) 1e6
application of nucleophiles different from
a
,
b-unsaturated ketones
sequential one. Indeed, the reactions of the nitroenamines 1aec
or esters, e.g., nitroenamines, is still not explored.
with ethyl glyoxylate and anilines afforded the racemic products
4aes along with some 2aec.
2. Results and discussion
First we prepared the imine 3a from p-anisidine and ethyl
glyoxylate according to literature procedure8 in DCM at ambient
temperature in the presence of molecular sieves with practically
quantitative yield. The reaction of ethyl glyoxylate and 3-
nitroaniline, however, took place only at elevated temperature in
toluene to afford 3b (Scheme 3). The aryliminoacetates 3a,b thus
obtained and used without further purification were then reacted
with the nitroenamine 1a resulting in the multisubstituted adducts
4a,b (Scheme 4).
Scheme 6. Three-component reaction with nitroenamines 1aec.
Based on NMR criteria, we reported3c,4,10 previously the Z con-
figuration of our starting compound 1a. As this configuration may
change under the reaction conditions applied, compound 4c was
subjected to selective NOE experiments. Upon irradiating the 2-H
atom a significant NOE increment was detected on the signal of
the 30-H2 atoms demonstrating their steric proximity and the un-
changed Z configuration.
In a study of the solvent dependence the best yields (up to 80%)
were observed in trifluoroethanol, mainly due to the distinguished
physicochemical properties of fluorous solvents,11 such as low nu-
cleophilicity, high polarity and strong hydrogen bond donating
ability. The reaction times were, however, strongly dependent on
the nature of the substituent at the aromatic ring. The compounds
prepared in the one-pot reaction are summarized in Table 1.
Scheme 3. Preparation of ethyl aryliminoacetates.
Table 1
Compounds 4aes prepared in one-pot reactions
Entry
R
n
Yield (%)
Reaction time
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4r
4s
4-OCH3
3-NO2
4-CH3
H
1
1
1
1
1
1
1
1
1
1
2
2
2
2
3
3
3
3
67
77
72
78
66
66
72
69
75
70
73
70
74
72
68
70
73
69
4
48
2
8
4
2-OCH3
Scheme 4. Reaction of nitroenamine 1a with aryliminoacetates.
3-CH3, 4-CH3
3-Cl, 4-Cl
4-CF3
4-OC6H5
4-CO2C2H5
3-CH3, 4-CH3
3-Cl, 4-Cl
3-NO2
4-CO2C2H5
3-CH3, 4-CH3
3-Cl, 4-Cl
3-NO2
4
24
48
1
28
4
26
48
30
5
24
48
30
As the aza-MBH reactions are usually catalyzed by tertiary
amines, the reaction was carried out in the presence of triethyl-
amine or DABCO, as well. It was however established that neither
the rate nor the conversion of the reactions was influenced by the
base remarkably.
Our earlier results showed that the adduct 2a underwent nu-
cleophilic substitution with alcohols.4 In an analogous trans-
formation 2a was converted into the substituted products 4b,c
using 3-nitro- and 4-methyl-anilines as nucleophiles. The reactions
were carried out in different solvents, such as acetonitrile, ethanol,
but the best results were achieved in trifluoroethanol. The reaction
times were long in both cases, but after 48 h 87% conversion for 4b
and 76% for 4c was detected (Scheme 5).
4-CO2C2H5
To get a deeper insight into the one-pot reaction, it was moni-
tored by HPLC measurements. First we established that approxi-
mately 80% of the nitroenamine was consumed in 20 min in the
three-component reaction of 1a and ethyl glyoxylate with 3-
nitroaniline, but only 2a was formed (Fig. 1). Due to the electron
withdrawing nitro group the formation of the imine 3b is much
slower than that of 2a. The diagram for the same reaction on
a longer time scale shows that 2a was consumed slowly, to give
finally compound 4b (Fig. 2) with 81% conversion after 48 h.
On the other hand, an experiment with aniline bearing electron
donating group at the aromatic ring gave different result. Using 4-
methylaniline, nitroenamine 1a was consumed in 1 h, and the ratio
of the products 4c/2a in the reaction mixture was 7:2, respectively.
Consequently, the formation of the imine and next, the final
Scheme 5. Preparation of 4b,c from 2a and anilines.
As both approaches outlined above led to the same products, we
attempted
Please cite this article in press as: Pilipecz, M. V.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.04.096
a
one-pot procedure9 (Scheme 6) instead of the

M.V. Pilipecz et al. / Tetrahedron xxx (2014) 1e6
3
predominantly the compound 2a will be formed, which can un-
dergo to a nucleophilic substitution with anilines to give the de-
sired adducts (Scheme 7).
Fig. 1. HPLC monitoring of the one-pot reaction with 3-nitroaniline.
Scheme 7. Two routes leading to the products of aza-MBH type.
Fig. 2. HPLC monitoring of the one-pot reaction with 3-nitroaniline.
3. Conclusion
product 4c was faster than that of 2a (Fig. 3), the amount of which
decreased slowly to give 4c with 78% yield after 48 h (Fig. 4).
In summary, a new one-pot catalyst-free synthesis for multi-
substituted ethyl propionates was developed starting from nitro-
enamines, ethyl glyoxylate and substituted anilines. It seems to be
obvious that the presence of the nitrogen in the activated alkene
increases its reactivity in these sequences, and explains the ob-
servation that the use of tertiary amines as catalysts does not in-
fluence the reaction rate remarkably. Our protocol offers
considerable benefits, like simple reactants, synthetic work carried
out on gram-scale and access to a large number of new multi-
functional compounds for further transformations to poly-
substituted heterocyclic scaffolds. An enantioselective approach to
the adducts 4 is in progress.
4. Experimental section
4.1. General methods
Fig. 3. HPLC monitoring of the one-pot reaction with 4-methylaniline.
The NMR signals of the products were assigned by compre-
hensive one- and two-dimensional NMR methods using widely
accepted strategies. 1H (500.1 MHz) and 13C (125.6 MHz) NMR
measurements were recorded at room temperature on a Bruker
Avance 500 spectrometer. Chemical shifts, given on the
d scale,
were referenced to the solvent (CDCl3: dC¼77.0 and dH¼7.27). In the
1D measurements (1H, 13C, DEPTQ, DEPT-135, sel-NOE), 64K data
points were used for the FID. The pulse programs (gradient-se-
lected HSQC, -HMBC) were taken from the Bruker software library.
The HRMS analyses were performed with an Agilent 5230 TOF in-
strument; ion source: ESI Jetstream. IR spectra were recorded on
a PerkineElmer 1600 FTIR spectrometer. HPLC separations were
made by Merck Hitachi instrument, with diode array detector, on
XTerra MS C18 4.6e100 mm column, using water/methanol eluent
with 0.05% trifluoroacetic acid.
Fig. 4. HPLC monitoring of the one-pot reaction with 4-methylaniline.
On the basis of the HPLC measurements it can be established
that the three-component reaction takes place in two different
ways. While electron donating substituents facilitate the formation
of the imine and the reaction affords directly the adduct of aza-
MBH type, electron withdrawing substituents slow down it and
4.2. Nitroenamines
Compounds 1aec used as starting materials were prepared
according to literature procedures12 from the corresponding cyclic
imino ethers and nitromethane.
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4
M.V. Pilipecz et al. / Tetrahedron xxx (2014) 1e6
4.3. Ethyl (2-hydroxy-3-nitro-3-pyrrolidin-20-ylidene)-pro-
pionate4 (2a)
2.90e2.80 (1Hþ1H, m, 30-H2), 2.25e2.10 (2H, m, 40-H2), 1.24 (3H, t, J
7.1 Hz, OCH2CH3); dC (125 MHz, CDCl3) 170.7 (C-1), 163.7 (C-20),
153.2 (C-400), 140.4 (C-100), 117.4 (C-3), 116.7 (C-200,600), 114.8 (C-
300,500), 61.9 (OCH2), 58.3 (C-2), 55.6 (400-OCH3), 48.8 (C-50), 32.4 (C-
30), 21.3 (C-40), 14.1 (OCH2CH3). HRMSeESI m/z [MþNa]þ calcd for
2-Nitromethylene-pyrrolidine 1a (320 mg, 2.5 mmol) and ethyl
glyoxylate (0.5 mL 50% solution in toluene, 2.5 mmol) were stirred
in EtOAc (10 mL) at ambient temperature for 15 min. The crystalline
substance formed was filtered out and recrystallized from EtOAc to
give 2a (518 mg, 90%) as a white crystalline solid, mp 111e112 ꢀC; dH
(500 MHz, CDCl3) 9.76 (1H, s, 10-NH), 4.78 (1H, d, J 6.7 Hz, 2-H), 4.24
(2H, q, J 7.2 Hz, OCH2), 3.87 (1H, d, J 6.7 Hz, 2-OH), 3.82 (2H, t, J
7.3 Hz, 50-H2), 3.07e2.93 (2H, m, 30-H2), 2.27e2.18 (2H, m, 40-H2),
1.26 (3H, t, J 7.2 Hz, OCH2CH3); dC (125 MHz, CDCl3) 171.6, 164.0,
117.8, 68.9, 62.2, 49.1, 32.3, 21.2, 14.1.
C16H21N3O5Na: 358.1373; found: 358.1379.
4.7.2. 3-Nitro-2-(3-nitro-phenylamino)-3-pyrrolidin-2-ylidene-pro-
pionic acid ethyl ester (4b). Yellow solid (674 mg, 77%), mp 137 ꢀC;
Rf (n-hexane/EtOAc 1:2) 0.49. nmax (KBr) 3367, 3347, 2985, 1747,
1
1717, 1610, 1353 cmꢁ1
;
dH H NMR (500 MHz, CDCl3) 9.84 (1H, s, 10-
NH), 7.55 (1H, d, J 7.5 Hz, 400-H), 7.35 (1H, s, 200-H), 7.28 (1H, dd, J 8.6
7.5 Hz, 500-H), 6.95 (1H, d, J 8.6 Hz, 600-H), 5.47 (1H, d, J 7.7 Hz, 2-NH),
5.03 (1H, d, J 7.7 Hz, 2-H), 4.23 (2H, q, J 7.1 Hz, OCH2), 3.82 (2H, t, J
7.3 Hz, 50-H2), 3.21e3.01 (2H, m, 30-H2), 2.35e2.23 (2H, m, 40-H2),
1.24 (3H, t, J 7.1 Hz, OCH2CH3); dC (125 MHz, CDCl3) 169.7 (C-1),
163.6 (C-20), 149.2 (C-300), 147.2 (C-100), 129.9 (C-500), 120.6 (C-600),
116.3 (C-3), 113.0 (C-400), 106.5 (C-200), 62.3 (OCH2), 55.9 (C-2), 49.0
(C-50), 32.7 (C-30), 21.4 (C-40), 14.1 (OCH2CH3). HRMSeESI m/z
[MþNa]þ calcd for C15H18N4O6Na: 373.1118; found: 373.1116.
4.4. Preparation of compounds 3a,b
p-Anisidine (124 mg, 1 mmol) was dissolved in DCM (5 mL),
ꢁ
molecular sieves (4 A, 0.5 g) and ethyl glyoxylate (0.2 mL, 1 mmol
50% solution in toluene) were added. The mixture was stirred for
2 h and the solvent was removed at reduced pressure to give 3a
practically in quantitative yield. Its 1H spectrum was identical as
described.8c Compound 3b was prepared in toluene (5 mL) from 4-
methyl-aniline (1 mmol) and ethyl glyoxylate in the presence of
molecular sieves. The mixture was heated at 100 ꢀC for 3 h then
evaporated. The oily products were used in the next step without
further purification.
4.7.3. 3-Nitro-2-(4-methyl-phenylamino)-3-pyrrolidin-2-ylidene-
propionic acid ethyl ester (4c). Yellow solid (574 mg, 72%), mp
136 ꢀC; Rf (EtOAc) 0.41. nmax (KBr) 3381, 2951, 1711, 1608, 1349,
1224 cmꢁ1 dH (500 MHz, CDCl3) 9.83 (1H, s, 10-NH), 6.98 (2H, d, J
;
8.3 Hz, 300,500-H), 6.58 (2H, d, J 8.3 Hz, 200,600-H), 5.10 (1H, d, J 8.0 Hz,
2-H), 4.90 (1H, d, J 8.0 Hz, 2-NH), 4.26e4.16 (2H, m, OCH2), 3.75 (2H,
t, J 7.3 Hz, 50-H2), 3.14e3.06 and 2.95e2.87 (1Hþ1H, m, 30-H2), 2.23
(3H, s, 400-CH3), 2.25e2.10 (2H, m, 40-H2), 1.24 (3H, t, J 7.1 Hz,
OCH2CH3); dC (125 MHz, CDCl3) 170.8 (C-1), 163.6 (C-20), 144.1 (C-
100), 129.8 (C-300,500), 128.1 (C-400), 117.5 (C-3), 114.6 (C-200,600), 61.8
(OCH2), 57.0 (C-2), 48.7 (C-50), 32.4 (C-30), 21.3 (C-40), 20.4 (400-CH3),
14.2 (OCH2CH3). HRMSeESI m/z [MþNa]þ calcd for C16H21N3O4Na:
342.1424; found: 342.1425.
4.5. General procedure for the preparation of compounds
4a,b
The solution of 1a (128 mg, 1 mmol) and crude 3a and 3b
(1 mmol) in 5 mL acetonitrile was stirred at room temperature for 3 h
and 12 h, respectively. After removal of the solvent 4a was obtained
as yellowish red residue, which was purified by column chroma-
tography on silica gel using EtOAc/hexane as eluent to yield the title
compounds as yellow solids (255 mg, 76%), mp 112 ꢀC. Compound 4b
was obtained as a solid after evaporation, which was crystallized
from EtOAc to give yellow crystals (210 mg, 60%), mp 135e136 ꢀC.
4.7.4. 3-Nitro-2-phenylamino-3-pyrrolidin-2-ylidene-propionic acid
ethyl ester (4d). Yellow solid (594 mg, 78%), mp 139 ꢀC; Rf (n-hex-
ane/EtOAc 1:2) 0.50. nmax (KBr) 3386, 2956, 1751, 1600, 1509,
1303 cmꢁ1 dH (500 MHz, CDCl3) 9.82 (1H, s, 10-NH), 7.15 (2H, t, J
;
4.6. Preparation of compounds 4b,c from 2a and anilines
8.0 Hz, 300,500-H), 6.72 (1H, t, J 8.0 Hz, 400-H), 6.62 (2H, d, J 8.0 Hz,
200,600-H), 5.10 (1H, m, 2-H), 5.06 (1H, s, 2-NH), 4.22e4.12 (2H, m,
OCH2), 3.70 (2H, t, J 7.3 Hz, 50-H2), 3.12e3.00 and 3.00e2.88
(1Hþ1H, m, 30-H2), 2.13e1.93 (2H, m, 40-H2), 1.21 (3H, t, J 7.1 Hz,
OCH2CH3); dC (125 MHz, CDCl3) 170.6 (C-1), 163.6 (C-20), 146.4 (C-
100), 129.2 (C-300,500), 118.6 (C-400), 117.2 (C-3), 114.0 (C-200,600), 61.9
(OCH2), 56.4 (C-2), 48.8 (C-50), 32.4 (C-30), 21.2 (C-40), 14.1
(OCH2CH3). HRMSeESI m/z [MþNa]þ calcd for C15H19N3O4Na:
328.1268; found: 328.1260.
Compound 2a (230 mg, 1 mmol) and aniline (1 mmol) were
dissolved in trifluoroethanol (4 mL) and the solution was stirred at
70 ꢀC for 48 h. The solvent was then removed at reduced pressure
and the residue was purified with column chromatography on silica
gel using EtOAc/hexane as eluent to give 4b (262 mg 75%) and 4c
(236 mg 74%).
4.7. General procedure for the one-pot synthesis of com-
pounds 4aes
4.7.5. 3-Nitro-2-(2-methoxy-phenylamino)-3-pyrrolidin-2-ylidene-
propionic acid ethyl ester (4e). Yellow solid (553 mg, 66%), mp
155 ꢀC; Rf (n-hexane/EtOAc 1:2) 0.47. nmax (KBr) 3424, 3312, 2930,
Nitroenamine 1aec (2.5 mmol), ethyl glyoxylate (0.55 mL 50%
solution in toluene, 2.75 mmol) and the corresponding aniline
(3.0 mmol) were stirred in 10 mL trifluoroethanol at 70 ꢀC until the
nitroenamine and/or the MBH product were consumed. The solvent
was then removed in vacuum and the crude product was purified
by column chromatography on silica gel using EtOAc/hexane as
eluent to give the crystalline product.
1748, 1612, 1358, 1226 cmꢁ1 dH (500 MHz, CDCl3) 9.84 (1H, s, 10-
;
NH), 6.81 (1H, t, J 7.7 Hz, 500-H), 6.78 (1H, d, J 7.7 Hz, 300-H), 6.71 (1H,
t, J 7.7 Hz, 400-H), 6.53 (1H, d, J 7.7 Hz, 600-H), 5.48 (1H, s, 2-NH), 5.28
(1H, s, 2-H), 4.26e4.16 (2H, m, OCH2), 3.85 (3H, s, 400-OCH3), 3.74
(2H, t, J 7.5 Hz, 50-H2), 3.12e3.02 and 2.90e2.80 (1Hþ1H, m, 30-H2),
2.25e2.10 (2H, m, 40-H2), 1.24 (3H, t, J 7.1 Hz, OCH2CH3); dC
(125 MHz, CDCl3) 170.7 (C-1), 163.7 (C-20), 147.6 (C-200), 136.1 (C-100),
121.1 (C-500), 118.0 (C-400), 117.3 (C-3), 111.4 (C-600), 110.1 (C-300), 61.8
(OCH2), 55.8 (C-2), 55.5 (200-OCH3), 48.6 (C-50), 32.1 (C-30), 21.3 (C-
40), 14.1 (OCH2CH3). HRMSeESI m/z [MþNa]þ calcd for
4.7.1. 3-Nitro-2-(4-methoxy-phenylamino)-3-pyrrolidin-2-ylidene-
propionic acid ethyl ester (4a). Yellow solid (560 mg, 67%), mp
113 ꢀC; Rf (n-hexane/EtOAc 1:2) 0.32. nmax (KBr) 3392, 3293, 2949,
1751, 1607, 1515, 1357 cmꢁ1
;
dH (500 MHz, CDCl3) 9.82 (1H, s, 10-
C16H21N3O5Na: 358.1381; found: 358.1373.
NH), 6.76 (2H, d, J 8.7 Hz, 300,500-H), 6.64 (2H, d, J 8.7 Hz, 200,600-H),
4.98 (1H, s, 2-H), 4.78 (1H, s, 2-NH), 4.26e4.16 (2H, m, OCH2), 3.74
(2H, t, J 7.5 Hz, 50-H2), 3.73 (3H, s, 400-OCH3), 3.12e3.02 and
4.7.6. 3-Nitro-2-(3,4-dimethyl-phenylamino)-3-pyrrolidin-2-
ylidene-propionic acid ethyl ester (4f). Yellow solid (549 mg, 76%);
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M.V. Pilipecz et al. / Tetrahedron xxx (2014) 1e6
5
mp 138 ꢀC; Rf (n-hexane/EtOAc 1:2) 0.51. nmax (KBr) 3383, 2961,
1752, 1707, 1606, 1512, 1235 cmꢁ1
dH (500 MHz, CDCl3) 9.84 (1H, s,
(C-100), 131.4 (C-300,500), 119.8 (C-400), 116.6 (C-3), 112.3 (C-200,600), 62.1
(OCH2), 60.2 (400-OCH2), 55.3 (C-2), 48.9 (C-50), 32.4 (C-30), 21.2 (C-
40), 14.3 (400-OCH2CH3), 14.0 (OCH2CH3). HRMSeESI m/z [MþNa]þ
calcd for C18H23N3O6Na: 400.1479; found: 400.1479.
;
10-NH), 6.93 (1H, d, J 8.0 Hz, 500-H), 6.49 (1H, d, J 2.3 Hz, H-200), 6.41
(1H, dd, J 8.0, 2.3 Hz, 600-H), 5.10 (1H, s, 2-H), 4.27e4.17 (2H, m,
OCH2), 3.76 (2H, t, J 7.3 Hz, 50-H2), 3.15e3.07 and 2.97e2.88
(1Hþ1H, m, 30-H2), 2.26e2.11 (2H, m, 40-H2), 1.24 (3H, t, J 7.1 Hz,
OCH2CH3); dC NMR (125 MHz, CDCl3) 170.8 (C-1), 163.6 (C-20), 144.5
(C-100), 133.7 (C-300), 130.3 (C-500), 126.9 (C-400), 117.6 (C-3), 116.5 (C-
200), 111.6 (C-600), 61.9 (OCH2), 56.9 (C-2), 48.7 (C-50), 32.4 (C-30), 21.4
(C-40), 20.0 (300-CH3), 18.7 (400-CH3), 14.2 (OCH2CH3). HRMSeESI m/z
[MþNa]þ calcd for C17H23N3O4Na: 356.1580; found: 356.1580.
4.7.11. 3-Nitro-2-(3,4-dimethyl-phenylamino)-3-piperidin-2-ylidene-
propionic acid ethyl ester (4k). Yellow solid (633 mg, 73%); mp 62 ꢀC;
Rf (cyclohexane/EtOAc 1:3) 0.40. nmax (KBr) 3393, 2935, 1748, 1602,
1509, 1337 cmꢁ1 dH (500 MHz, CDCl3) 11.91 (1H, s, 10-NH), 6.93 (1H,
;
d, J 8.0 Hz, 500-H), 6.50 (1H, d, J 2.5 Hz, 200-H), 6.42 (1H, dd, J 8.0 2.5 Hz,
H-600), 5.10 (1H, s, 2-H), 4.89 (1H, s, 2-NH), 4.20 (2H, q, J 7.1 Hz, OCH2),
3.58e3.46 (2H, m, 60-H2), 2.89e2.81 and 2.70e2.62 (1Hþ1H, m, 30-
H2), 2.18 (3H, s, 300-CH3), 2.15 (3H, s, 400-CH3) 1.95e1.80 (4H, m, 40-H2
and 50-H2), 1.23 (3H, t, J 7.1 Hz, OCH2CH3); dC (125 MHz, CDCl3) 170.9
(C-1), 160.5 (C-20), 144.8 (C-100), 137.4 (C-300), 130.3 (C-500), 126.8 (C-
400), 119.8 (C-3), 116.4 (C-200),111.5 (C-600), 61.8 (OCH2), 55.4 (C-2), 42.1
(C-60), 26.3 (C-30), 20.6 (C-50), 20.0 (300-CH3),18.8 (C-40),18.7 (400-CH3),
14.2 (OCH2CH3). HRMSeESI m/z [MþNa]þ calcd for C18H25N3O4Na:
370.1737; found: 370.1734.
4.7.7. 3-Nitro-2-(3,4-dichlor-phenylamino)-3-pyrrolidin-2-ylidene-
propionic acid ethyl ester (4g). Yellow solid (673 mg, 72%); mp
145 ꢀC; Rf (n-hexane/EtOAc 1:2) 0.55. nmax (KBr) 3379, 3315, 2985,
1714, 1611, 1536, 1319 cmꢁ1 dH (500 MHz, CDCl3) 9.84 (1H, s, 10-
;
NH), 7.20 (1H, d, J 8.6 Hz, 500-H), 6.69 (1H, d, J 2.7 Hz, H-200), 6.48 (1H,
dd, J 8.6 2.7 Hz, 600-H), 5.13 (1H, s, 2-NH), 5.00 (1H, s, 2-H), 4.22 (2H,
q, J 7.1 Hz, OCH2), 3.81 (2H, t, J 7.4 Hz, 50-H2), 3.16e3.02 and
3.00e2.85 (1Hþ1H, m, 30-H2), 2.31e2.16 (2H, m, 40-H2), 1.25 (3H, t, J
7.1 Hz, OCH2CH3) dC (125 MHz, CDCl3) 170.0 (C-1),163.4 (C-20),146.0
(C-100), 132.9 (C-300), 130.8 (C-500), 121.2 (C-400), 116.6 (C-3), 115.1 (C-
200),113.8 (C-600), 62.3 (OCH2), 56.2 (C-2), 48.9 (C-50), 32.5 (C-30), 21.4
(C-40), 14.1 (OCH2CH3). HRMSeESI m/z [MþNa]þ calcd for
4.7.12. 3-Nitro-2-(3,4-dichlor-phenylamino)-3-piperidin-2-ylidene-
propionic acid ethyl ester (4l). Yellow solid (679 mg, 70%); mp 77 ꢀC;
Rf (cyclohexane/EtOAc 1:3) 0.51. nmax (KBr) 3393, 2956, 2871, 1747,
1595, 1338 cmꢁ1 dH (500 MHz, CDCl3) 11.87 (1H, s, 10-NH), 7.20 (1H,
;
C
15H17Cl2N3O4Na: 396.0488; found: 396.0491.
d, J 8.7 Hz, 500-H), 6.70 (1H, d, J 2.8 Hz, 200-H), 6.49 (dd, J 8.7, 2.8 Hz,
1H, H-600), 5.15 (1H, s, 2-NH), 5.01 (1H, s, 2-H), 4.21 (2H, q, J 7.1 Hz,
OCH2), 3.61e3.51 (2H, m, 60-H2), 2.88e2.80 and 2.66e2.60 (1Hþ1H,
m, 30-H2), 1.98e1.85 (4H, m, 40-H2 and 50-H2), 1.24 (t, J 7.1 Hz, 3H,
OCH2CH3); dC (125 MHz, CDCl3) 170.1 (C-1), 160.3 (C-20), 146.4 (C-
100), 132.9 (C-300), 130.8 (C-500), 121.2 (C-400), 118.9 (C-3), 115.0 (C-200),
113.8 (C-600), 62.1 (OCH2), 54.7 (C-2), 42.2 (C-60), 26.4 (C-30), 20.5 (C-
50), 18.8 (C-40), 14.2 (OCH2CH3). HRMSeESI m/z [MþNa]þ calcd for
4.7.8. 3-Nitro-2-(4-trifluormethyl-phenylamino)-3-pyrrolidin-2-
ylidene-propionic acid ethyl ester (4h). Yellow solid (642 mg, 69%);
mp 128 ꢀC; Rf (n-hexane/EtOAc 1:2) 0.57. nmax (KBr) 3379, 3315,
2985, 1714, 1611, 1536, 1319 cmꢁ1
; dH (500 MHz, CDCl3) 9.85 (1H, s,
10-NH), 7.40 (2H, d, J 8.2 Hz, 300,500-H), 6.63 (2H, d, J 8.2 Hz, 200,600-H),
5.36 (1H, d, J 8.3 Hz, 2-NH), 5.18 (1H, d, J 8.3 Hz, 2-H), 4.28e4.18 (2H,
m, OCH2), 3.79 (2H, t, J 7.2 Hz, 50-H2), 3.14e3.05 and 2.97e2.89
(1Hþ1H, m, 30-H2), 2.28e2.17 (2H, m, 40-H2), 1.25 (3H, t, J 7.1 Hz,
OCH2CH3); dC (125 MHz, CDCl3) 170.1 (C-1), 163.5 (C-20), 148.9 (C-
100), 126.7 (q, J 3.5 Hz, C-300,500), 124.7 (q, J 270 Hz, 400-CF3),120.0 (q, J
32.5 Hz, C-400), 116.7 (C-3), 112.8 (C-200,600), 62.3 (OCH2), 55.5 (C-2),
48.8 (C-50), 32.4 (C-30), 21.3 (C-40), 14.1 (OCH2CH3). HRMSeESI m/z
[MþNa]þ calcd for C16H18F3N3O4Na: 396.1141; found: 396.1136.
C16H19Cl2N3O4Na: 410.0646; found: 410.0648.
4.7.13. 3-Nitro-2-(3-nitro-phenylamino)-3-piperidin-2-ylidene-pro-
pionic acid ethyl ester (4m). Yellow solid (673 mg, 74%); mp 97 ꢀC; Rf
(cyclohexane/EtOAc 1:3) 0.44. nmax (KBr) 3358, 3131, 2975, 1734,
1605, 1521, 1345 cmꢁ1 dH (500 MHz, CDCl3) 11.85 (1H, s, 10-NH), 7.54
;
(1H, dd, J 8.1, 2.2 Hz, 400-H), 7.35 (1H, t, J 2.2 Hz, 200-H), 7.27 (1H, t, J
8.1 Hz, 500-H), 6.94 (1H, dd, J 8.0, 2.2 Hz, H-600), 5.48 (1H, s, 2-NH), 5.10
(1H, s, 2-H), 4.20 (2H, q, J 7.1 Hz, OCH2), 3.60e3.52 (2H, m, 60-H2),
2.92e2.84 and 2.76e2.68 (1Hþ1H, m, 30-H2),1.96e1.85 (4H, m, 40-H2
and 50-H2), 1.22 (3H, t, J 7.1 Hz, OCH2CH3); dC (125 MHz, CDCl3) 169.8
(C-1), 160.5 (C-20), 149.2 (C-300), 147.7 (C-100), 129.9 (C-500), 120.5 (C-
600),118.5 (C-3),112.9 (C-400),106.4 (C-200), 62.1 (OCH2), 54.1 (C-2), 42.2
(C-60), 26.5 (C-30), 20.5 (C-50), 18.7 (C-40), 14.0 (OCH2CH3). HRMSeESI
m/z [MþNa]þ calcd for C16H20N4O6Na: 387.1275; found: 387.1279.
4.7.9. 3-Nitro-2-(4-phenoxy-phenylamino)-3-pyrrolidin-2-ylidene-
propionic acid ethyl ester (4i). Yellow solid (743 mg, 75); mp 158 ꢀC;
Rf (n-hexane/EtOAc 1:2) 0.51. nmax (KBr) 3396, 3314, 2972, 1734,
1601, 1356, 1220 cmꢁ1 9.85 (1H, s, 10-NH),
; dH (500 MHz, CDCl3): d
7.28 (2H, t, J 7.5 Hz, meta), 7.02 (1H, t, J 7.5 Hz, para), 6.93 (2H, d, J
7.5 Hz, ortho), 6.89 (2H, d, J 8.9 Hz, 300,500-H), 6.65 (2H, d, J 8.9 Hz,
200,600-H), 5.07 (1H, d, J 7.9 Hz, 2-H), 4.98 (1H, d, J 7.9 Hz, 2-NH),
4.27e4.19 (2H, m, OCH2), 3.79 (2H, t, J 7.3 Hz, 50-H2), 3.15e3.07 and
2.96e2.88 (1Hþ1H, m, 30-H2), 2.28e2.14 (2H, m, 40-H2), 1.25 (3H, t, J
7.1 Hz, OCH2CH3); dC (125 MHz, CDCl3) 170.7 (C-1), 163.6 (C-20),
158.6 (C-ipso), 149.0 (C-400), 142.9 (C-100), 129.5 (C-meta), 122.2 (C-
para), 121.0 (C-ortho), 117.3 (C-3), 117.4 (C-200,600), 115.7 (C-300,500),
62.0 (OCH2), 57.3 (C-2), 48.8 (C-50), 32.4 (C-30), 21.4 (C-40), 14.2
(OCH2CH3). HRMSeESI m/z [MþNa]þ calcd for C21H23N3O5Na:
420.1530; found: 420.1516.
4.7.14. 4-(1-Ethoxycarbonyl-2-nitro-2-piperidin-2-ylidene-ethyl-
amino)-benzoic acid ethyl ester (4n). Yellow solid (704 mg, 72%);
mp 173e174 ꢀC; Rf (cyclohexane/EtOAc 1:3) 0.45. nmax (KBr) 3404,
3367, 2978, 1718, 1699, 1601, 1526, cmꢁ1
; dH (500 MHz, CDCl3) 11.83
(s, 1H, 10-NH), 7.84 (2H, d, J 8.7 Hz, 300,500-H), 6.58 (2H, d, J 8.7 Hz,
200,600-H), 5.48 (1H, s, 2-NH), 5.16 (1H, s, 2-H), 4.28 (2H, q, J 7.1 Hz,
400-OCH2), 4.18 (2H, q, J 7.1 Hz, OCH2), 3.53e3.47 (2H, m, 60-H2),
2.86e2.77 and 2.64e2.56 (1Hþ1H, m, 30-H2), 1.90e1.78 (4H, m, 40-
H2 and 50-H2), 1.33 (3H, t, J 7.1 Hz, 400-OCH2CH3), 1.20 (3H, t, J 7.1 Hz,
OCH2CH3); dC (125 MHz, CDCl3) 170.0 (C-1), 166.5 (400-C]O), 160.4
(C-20), 150.5 (C-100), 131.4 (C-300,500), 119.7 (C-400), 118.8 (C-3), 112.3
(C-200,600), 61.9 (OCH2), 60.1 (400-OCH2), 53.7 (C-2), 42.1 (C-60), 26.3
(C-30), 20.4 (C-50), 18.6 (C-40), 14.3 (400-OCH2CH3), 14.0 (OCH2CH3).
HRMSeESI m/z [MþNa]þ calcd for C19H25N3O6Na: 414.1635; found:
414.1630.
4.7.10. 4-(1-Ethoxycarbonyl-2-nitro-2-pyrrolidin-2-ylidene-ethyl-
amino)-benzoic acid ethyl ester (4j). Yellow solid (776 mg, 70%); mp
159 ꢀC; Rf (n-hexane/EtOAc 1:2) 0.44. nmax (KBr) 3354, 2938, 1702
(unresolved), 1601, 1380, 1230 cmꢁ1
; dH (500 MHz, CDCl3) 9.82 (1H,
s, 10-NH), 7.85 (2H, d, J 8.8 Hz, 300,500-H), 6.57 (2H, d, J 8.8 Hz, 200,600-
H), 5.46 (1H, s, 2-NH), 5.15 (1H, s, 2-H), 4.29 (2H, q, J 7.1 Hz, 400-
OCH2), 4.24e4.16 (2H, m, OCH2), 3.75 (2H, t, J 7.3 Hz, 50-H2),
3.12e3.03 and 2.97e2.88 (1Hþ1H, m, 30-H2), 2.24e2.12 (2H, m, 40-
H2), 1.33 (3H, t, J 7.1 Hz, 400-OCH2CH3), 1.24 (3H, t, J 7.1 Hz, OCH2CH3);
dC (125 MHz, CDCl3) 170.0 (C-1), 166.5 (400-C]O), 163.5 (C-20), 150.1
4.7.15. 3-Azepan-2-yilidene-3-nitro-(3,4-dimethyl-phenylamino)-
propionic acid ethyl ester (4o). Yellow solid (613 mg, 68%); mp
Please cite this article in press as: Pilipecz, M. V.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.04.096

6
M.V. Pilipecz et al. / Tetrahedron xxx (2014) 1e6
113 ꢀC; Rf (cyclohexane/EtOAc 1:3) 0.72. nmax (KBr) 3402, 3377,
2933, 1749, 1591, 1343 cmꢁ1 dH (500 MHz, CDCl3) 11.62 (1H, s, 10-
(OCH2), 60.2 (400-OCH2), 54.9 (C-2), 45.0 (C-70), 29.70 (C-50), 29.65
(C-30), 27.7 (C-60), 23.8 (C-40), 14.4 (400-OCH2CH3), 14.1 (OCH2CH3).
HRMSeESI m/z [MþNa]þ calcd for C20H27N3O6Na: 428.1792; found:
428.1792.
;
NH), 6.92 (1H, d, J 8.2 Hz, 500-H), 6.46 (1H, d, J 2.3 Hz, 200-H), 6.38 (1H,
dd, J 8.2, 2.3 Hz, H-600), 5.46 (1H, s, 2-H), 4.87 (1H, s, 2-NH),
4.27e4.15 (2H, m, OCH2), 3.57e3.50 (2H, m, 70-H2), 2.78e2.71 (2H,
m, 30-H2), 2.13 (3H, s, 400-CH3), 2.17 (3H, s, 300-CH3),1.85e1.75 (2H, m,
50-H2), 1.75e1.61 (4H, m, 40-H2 and 60-H2), 1.25 (3H, t, J 7.1 Hz,
OCH2CH3); dC (125 MHz, CDCl3) 171.2 (C-1), 166.2 (C-20), 144.5 (C-
100), 137.3 (C-300), 130.2 (C-500), 126.6 (C-400), 120.2 (C-3), 116.2 (C-200),
111.4 (C-600), 61.8 (OCH2), 55.4 (C-2), 44.9 (C-70), 29.7 and 29.6 (C-50
and C-30), 27.7 (C-60), 23.8 (C-40), 19.9 (300-CH3), 18.6 (400-CH3), 14.1
(OCH2CH3). HRMSeESI m/z [MþNa]þ calcd for C19H27N3O4Na:
384.1895; found: 384.1893.
Acknowledgements
ꢀ
Financial support from the Veterinary Faculty of the Szent Istvan
University (KK KF 12054) is gratefully acknowledged. The authors
ꢀ
ꢀ
ꢀ
are indebted to Valeria M. Szekely, Klara M. Ocskay and Ferenc
ꢀ
Csato for their technical help.
References and notes
4.7.16. 3-Azepan-2-yilidene-3-nitro-(3,4-dichlor-phenylamino)-pro-
pionic acid ethyl ester (4p). Yellow solid (701 mg, 70%); mp
105e107 ꢀC; Rf (cyclohexane/EtOAc 1:3) 0.72. nmax (KBr) 3354, 2945,
ꢀ
1. (a) Erian, A. W. Chem. Rev. 1993, 93, 1991; (b) Vincze, Z.; Nemes, P.; Balazs, B.;
ꢀ
Toth, G.; Scheiber, P. Synlett 2004, 1023; (c) Vincze, Z.; Mucsi, Z.; Scheiber, P.;
1736, 1585, 1342, 1221 cmꢁ1 dH (500 MHz, CDCl3) 11.58 (1H, s, 10-
;
Nemes, P. Eur. J. Org. Chem. 2008, 6, 1092; (d) Vincze, Z.; Nemes, P. Tetrahedron
2011, 67, 3380; (e) Vincze, Z.; Nemes, P. Tetrahedron 2013, 69, 6269; (f) Cheng,
Y.; Huang, Z.-T.; Wang, M.-X. Curr. Org. Chem. 2004, 8, 325.
2. (a) Altug, C.; Elliott, M. C.; Kariuki, B. M.; Rorstad, T.; Zaal, M.; Dueruest, Y. Org.
Biomol. Chem. 2010, 8, 4978; (b) Paulvannan, K.; Stille, J. R. J. Org. Chem. 1994, 59,
1613; (c) Kim, J. H.; Lee, S. G.; Shin, H. J. Org. Chem. 2012, 77, 1560; (d) Altug, C.;
Elliott, M. C.; Dueruest, Y. Tetrahedron Lett. 2009, 50, 7392.
NH), 7.16 (1H, d, J 8.7 Hz, 500-H), 6.66 (1H, d, J 2.8 Hz, 200-H), 6.44 (1H,
dd, J 8.7, 1.8 Hz, H-600), 5.39 (1H, s, 2-H), 5.17 (1H, s, 2-NH), 4.25e4.15
(2H, m, OCH2), 3.59e3.54 (2H, m, 70-H2), 2.77e2.68 (2H, m, 30-H2),
1.86e1.77 (2H, m, 50-H2), 1.74e1.64 (4H, m, 40-H2 and 60-H2), 1.25
(3H, t, J 7.1 Hz, OCH2CH3); dC (125 MHz, CDCl3) 170.4 (C-1), 166.2 (C-
20), 145.9 (C-100), 132.7 (C-300), 130.7 (C-500), 120.9 (C-400), 119.2 (C-3),
114.8 (C-200), 113.6 (C-600), 62.2 (OCH2), 55.6 (C-2), 45.0 (C-70), 29.67
and 29.62 (C-50 and C-30), 27.6 (C-60), 23.9 (C-40), 14.1 (OCH2CH3).
HRMSeESI m/z [MþNa]þ calcd for C17H21Cl2N3O4Na: 424.0801;
found: 424.0798.
3. (a) Felluga, F.; Pitacco, G.; Visintin, C.; Valentin, E. Helv. Chim. Acta 1997, 80,
1457; (b) Hutchinson, I. S.; Matlin, S. A.; Mete, A. Tetrahedron Lett. 2001, 42,
1773; (c) Pilipecz, M. V.; Varga, T. R.; Scheiber, P.; Mucsi, Z.; Favre-Mourgues, A.;
ꢀ
ꢀ
Boros, S.; Balazs, L.; Toth, G.; Nemes, P. Tetrahedron 2012, 68, 5547.
4. Pilipecz, M. V.; Mucsi, Z.; Nemes, P.; Scheiber, P. Heterocycles 2007, 71, 1919.
5. (a) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653; (b) Basavaiah, D. P.;
Rao, D.; Hyma, R. S. Tetrahedron 1996, 52, 8001; (c) Basavaiah, D.; Satyanar-
ayana, T.; Rao, A. J. Chem. Rev. 2003, 103, 811; (d) Declerck, V.; Martinez, J.;
Lamaty, F. Chem. Rev. 2009, 109, 1; (e) Shi, M.; Wang, F.-J.; Zhao, M.-X.; Wei, Y.
The Chemistry of the MoritaeBayliseHillman Reaction. RSC Catalysis Series No. 8;
Royal Society of Chemistry: Cambridge, 2011, and references therein;
4.7.17. 3-Azepan-2-yilidene-3-nitro-(3-nitro-phenylamino)-pro-
pionic acid ethyl ester (4r). Yellow solid (734 mg, 73%); mp
159e160 ꢀC; Rf (cyclohexane/EtOAc 1:3) 0.69. nmax (KBr) 3402,
ꢀ
(f) Mansilla, J.; Saa, J. M. Molecules 2010, 15, 709; (g) Shi, M.; Xu, Y.-M. Angew.
Chem., Int. Ed. 2002, 41, 4507; (h) Shi, M.; Xu, Y.-M.; Shi, Y.-L. Chem.dEur. J.
2005, 11, 1794; (i) Shi, M.; Chen, L.-H. Chem. Commun. 2003, 1310; (j) Shi, M.;
Chen, L.-H.; Li, C.-Q. J. Am. Chem. Soc. 2005, 127, 3790; (k) Shi, Y.-L.; Shi, M. Adv.
Synth. Catal. 2007, 349, 2129; (l) Qi, M.-J.; Ai, T.; Shi, M.; Li, G. Tetrahedron 2008,
64, 1181; (m) Guan, X.-Y.; Jiang, Y.-Q.; Shi, M. Eur. J. Org. Chem. 2008, 2150; (n)
Guan, X.-Y.; Wei, Y.; Shi, M. Eur. J. Org. Chem. 2010, 4098; (o) Pei, W.; Wei, H.-X.;
Li, G. Chem. Commun. 2002, 2412; (p) Pei, W.; Wei, H.-X.; Li, G. Chem. Commun.
2002, 1856; (q) Langer, P. Angew. Chem., Int. Ed. 2000, 39, 3049; (r) Masson, G.;
Housseman, C.; Zhu, J.-P. Angew. Chem., Int. Ed. 2007, 46, 4614; (s) Basavaiah, D.;
Rao, K. V.; Reddy, R. J. Chem. Soc. Rev. 2007, 36, 1581; (t) Shi, Y.-L.; Shi, M. Eur. J.
Org. Chem. 2007, 2905; (u) Singh, V.; Batra, S. Tetrahedron 2008, 64, 4511; (v)
Wei, Y.; Shi, M. Acc. Chem. Res. 2010, 43, 1005; (z) Yin, W.; Shi, M. Chem. Rev.
2013, 113, 6659.
2934,1746, 1585,1532,1343 cmꢁ1
; dH (500 MHz, CDCl3) 11.57 (1H, s,
10-NH), 7.52 (1H, dd, J 8.0, 1.8 Hz, 400-H), 7.33 (1H, t, J 1.8 Hz, 500-H),
7.25 (1H, t, J 8.0 Hz, 500-H), 6.90 (1H, dd, J 8.0, 1.8 Hz, H-600), 5.47 (1H,
s, 2-NH), 5.43 (1H, s, 2-H), 4.27e4.16 (2H, m, OCH2), 3.64e3.54 (2H,
m, 70-H2), 2.86e2.78 (2H, m, 30-H2), 1.89e1.79 (2H, m, 50-H2),
1.79e1.63 (4H, m, 40-H2 and 60-H2),1.24 (3H, t, J 7.1 Hz, OCH2CH3); dC
(125 MHz, CDCl3) 170.0 (C-1), 166.2 (C-20), 149.2 (C-300), 147.2 (C-100),
129.9 (C-500), 120.2 (C-600), 119.0 (C-3), 112.8 (C-400), 106.6 (C-200),
62.3 (OCH2), 55.4 (C-2), 45.1 (C-70), 29.74 and 29.67 (C-50 and C-30),
27.6 (C-60), 23.9 (C-40), 14.1 (OCH2CH3). HRMSeESI m/z [MþNa]þ
calcd for C17H22N4O6Na: 401.1431; found: 401.1435.
6. (a) Shi, M.; Xu, Y.-M. Eur. J. Org. Chem. 2002, 696; (b) Rastogi, N.; Mohan, R.;
Panda, D.; Mobin, S. M.; Namboothiri, I. N. N. Org. Biomol. Chem. 2006, 4, 3211;
(c) Bertenshaw, S.; Kahn, M. Tetrahedron Lett. 1989, 30, 2731; (d) Shi, M.; Xu, Y.-
M. J. Org. Chem. 2004, 69, 417.
4.7.18. 4-(2-Azepan-2-yliden-1-ethoxycarbonyl-2-nitro-ethyl-
amino)-benzoic acid ethyl ester (4s). Yellow solid (697 mg, 69%); mp
72 ꢀC; Rf (cyclohexane/EtOAc 1:3) 0.66. nmax (KBr) 3402, 2932, 1747,
7. (a) Gao, J.; Ma, G.-N.; Li, Q.-J.; Shi, M. Tetrahedron Lett. 2006, 47, 7685; (b)
Madhavan, S.; Shanmugam, P. Org. Lett. 2011, 13, 1590.
8. (a) Trost, B. M.; Marrs, C. M. J. Am. Chem. Soc. 1993, 115, 6636; (b) Sharma, S. D.;
Kanwar, S.; Rajpoot, S. J. Heterocycl. Chem. 2006, 43, 11; (c) Cobb, A. J. A.; Shaw,
D. M.; Longbottom, D. A.; Gold, J. B.; Ley, S. V. Org. Biomol. Chem. 2005, 3, 84.
9. Shi, M.; Zhao, G.-L. Tetrahedron Lett. 2002, 43, 9171.
1700, 1607, 1345 cmꢁ1 dH (500 MHz, CDCl3) 11.57 (1H, s, 10-NH),
;
7.85 (2H, d, J 8.7 Hz, 300,500-H), 6.55 (2H, d, J 8.7 Hz, 200,600-H), 5.56
(1H, s, 2-H), 5.46 (1H, s, 2-NH), 4.30 (2H, q, J 7.1 Hz, 400-OCH2),
4.27e4.16 (2H, m, OCH2), 3.58e3.53 (2H, m, 70-H2), 2.78e2.70 (2H,
m, 30-H2), 1.85e1.75 (2H, m, 50-H2), 1.75e1.62 (4H, m, 40-H2 and 60-
H2),1.34 (3H, t, J 7.1 Hz, 400-OCH2CH3), 1.24 (3H, t, J 7.1 Hz, OCH2CH3);
dC (125 MHz, CDCl3) 170.4 (C-1), 166.6 (400-C]O), 166.1 (C-20), 150.0
(C-100), 131.5 (C-300,500), 119.8 (C-400), 119.3 (C-3), 112.3 (C-200,600), 62.2
ꢀ
10. (a) Duddeck, H.; Dietrich, W.; Toth, G. Structure Elucidation by Modern NMR;
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Springer-Steinkopff: Darmstadt, 1998; (b) Pretsch, E.; Toth, G.; Munk, M. E.;
Badertscher, M. Computer-aided Structure Elucidation. Spectra Interpretation and
Structure Generation; Wiley-VCH: Weinheim, 2002.
€
€
11. Berkessel, A.; Adrio, J. A.; Huttenhain, D.; Neudorfl, J. M. J. Am. Chem. Soc. 2006,
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12. Pilipecz, M. V.; Varga, T. R.; Mucsi, Z.; Scheiber, P.; Nemes, P. Tetrahedron 2008,
45, 5545 and references therein.
Please cite this article in press as: Pilipecz, M. V.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.04.096