β-Nitroacrylates as key starting materials for the one-pot synthesis of densely functionalized penta-substituted anilines

Article abstract of DOI:10.1016/j.tet.2012.07.065

The reaction of ylidene malononitriles with β-nitroacrylates, in Et₃N/MeCN, affords the one-pot synthesis of a new class of penta-substituted, densely functionalized anilines in satisfactory to good overall yields. The method represents a very important improvement of the recent strategy for the preparation of anilines from conjugated nitroalkenes.

Full text of DOI:10.1016/j.tet.2012.07.065

Tetrahedron 68 (2012) 8231e8235
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b-Nitroacrylates as key starting materials for the one-pot synthesis of densely
functionalized penta-substituted anilines
Serena Gabrielli a, Alessandro Palmieri a, Deepak S. Panmand a, Daniela Lanari b, Luigi Vaccaro b,
,
Roberto Ballini a
*
a “Green Chemistry Group,” School of Science and Technology, Chemistry Division, University of Camerino, Via S. Agostino 1, 62032 Camerino (MC), Italy
b Laboratory of Green Synthetic Organic Chemistry, CEMIN e Chemistry Department, University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 May 2012
Received in revised form 19 June 2012
Accepted 17 July 2012
Available online 23 July 2012
The reaction of ylidene malononitriles with b-nitroacrylates, in Et3N/MeCN, affords the one-pot synthesis
of a new class of penta-substituted, densely functionalized anilines in satisfactory to good overall yields.
The method represents a very important improvement of the recent strategy for the preparation of
anilines from conjugated nitroalkenes.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Anilines
b
-Nitroacrylates
One-pot synthesis
Ylidene malononitriles
Conjugate addition
NH2
NO2
1) Et3N, CH2Cl2
NC CN
1. Introduction
NC
R
2
+
2) EtONa, CH3CN, air
R
R1
(eq. 1)
NO2
R2
R
ref. 5
Organic compounds featuring the amino group find widespread
occurrence due to their biological and other practical applica-
tions.1,2 In this context, of particular interest are aromatic amines
because they are found in biologically active natural products,
common pharmaceuticals, dyestuffs, materials with conductive and
emissive properties, and ligands for transition-metal-catalyzed
reactions. This is the reason why much effort has been spent on
methods to prepare aromatic amines.3,4
R1
1
2
3
Ar
R
CN
NC CN
NO2
Ar1
Et3N/CH2Cl2
ref. 6
+
R
(eq. 2)
NH2
Ar1
Ar
R1
O
R1
O
3'
1'
2'
Scheme 1. General procedures for the synthesis of anilines from nitroalkenes.
The main synthetic procedures for their preparation range from
classical methods, such as nitration and reduction of arenes, direct
displacement of halogens at high temperature, palladium-
mediated chemistry, modern transition-metal-catalyzed pro-
cesses, and improved copper-catalyzed processes. However, very
recently, two elegant and innovative procedures, starting from
conjugated nitroalkenes and vinyl malononitriles, have been
reported.5,6 By the latest methods it is possible to construct, di-
rectly, the aromatic ring and the amino group, giving rise to the
desired anilines (Scheme 1).
The first procedure (Eq. 1)5 only works with mono-substituted
nitroalkenes 2 (mainly conjugated with an aromatic system), and
needs the employment of oxidative conditions and of two different
solvent/base systems giving access to tetra- or penta-substituted o-
nitro-o’-cyano-aniline derivatives 3. The second method6 is de-
voted to the synthesis of dibenzopyran derivatives 3’ and seems to
be limited to the use of conjugated vinyl malonitriles 1’ and con-
jugated nitroalkenes 2’, both essential for the aromatization to the
aniline ring by nitrous acid elimination on the final step. In addi-
tion, these procedures require the use of CH2Cl2, one of the most
undesirable solvents.7
Thus, these promising approaches merit further investigations
in order to enlarge the panorama of their possible applications.
* Corresponding author. Tel.: þ39 0737 402 270; fax: þ39 0737 402 297; e-mail
address: roberto.ballini@unicam.it (R. Ballini).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.065

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S. Gabrielli et al. / Tetrahedron 68 (2012) 8231e8235
2. Results and discussion
is possible to introduce a nitro group in the o-position and an alkyl
group in the m-position (7, Eq. 1), (ii) from nitrocromenes6 it is
possible to insert a benzyl group in the o-position and an aryl
In the last few years, it has been demonstrated that b-nitro-
acrylates are an emerging, more reactive and versatile class of
functionalized nitroalkene, by which a variety of important targets
can be obtained under easier and more efficient methodologies.8
substituent in the m-position (8, Eq. 2) while (iii) from b-nitro-
acrylates (9, our protocol, Eq. 3) it is possible to introduce an alkyl
group in the o-position and an ester functionality in the m-position.
In conclusion, this important synthetic improvement expands
both the variety of the molecular structures of the obtained anilines
and the applications of b-nitroacrylates as strategic starting mate-
rials in organic synthesis.
Thus, during our ongoing studies on
b-nitroacrylates we envis-
aged that the employment of these compounds, as a partner-
reagent of ylidene malononitriles, would provide a new class of
functionalized anilines and, in this sense, we investigated a model
reaction between the ylidene 4a and the
(Scheme 2) under different promoter/solvent systems.
b-nitroacrylate 5a
4. Experimental
4.1. General
NH
NC CN
+
NC CN
COOEt
NC
NO2
NO2
promoter
1H NMR were recorded at 400 MHz on a Varian Mercury Plus 400.
13C NMR were recorded at 100 MHz. Microanalyses were performed
with a CHNSeO analyzer Model EA 1108 from Fisons Instruments.
Mass spectra were performed with a GC/MS system Agilent Tech-
nologies 6850 II/5973 Inert by means of the EI technique (70 eV). IR
spectra were recorded with a PerkineElmer Paragon 500 FT-IR. Yili-
dene malononitriles 4aef were synthetized according to the meth-
COOEt
H
solvent
h1
NO2
COOEt
5a
4a
A
B
h2
NH2
NC
odology reported from Chen et al. in 2005.9
b-nitroacrylates 5aei
COOEt
6aa
were synthesized according to our previously reported procedure.8a
Scheme 2. Selected reactions for the synthesis of anilines.
4.2. General procedure for the preparation of anilines 6
As reported in Table 1, the best result was obtained using 1 equiv
of Et3N (in acetonitrile) by which the target compound 6aa could be
prepared in 70% overall yield and in a one-pot process.
Triethylamine (TEA, 0.15 mmol) was added to a stirred, cooled
(ice-water) solution of ylidene malonitrile derivative 4 (1 mmol)
and b-nitroacrylate 5 (1 mmol) in acetonitrile (2.5 mL). The mixture
Encouraged by this result, and in order to assess the generality
of our method, a number of different ylidene malononitriles 4 and
was allowed to reach room temperature and left for the appropriate
time (Table 2). Then, further 2.5 mL of MeCN and TEA (0.85 mmol)
were added and the mixture was gradually heated and refluxed for
the appropriate time (Table 2). After cooling, the reaction mixture
was quenched with 2 M HCl (10 mL), extracted with EtOAc and the
organic layer dried over Na2SO4. After removal of the solvent at
reduced pressure, the crude product was purified by flash chro-
matography column (hexane/EtOAc), allowing the pure aniline 6.
b-nitroacrylates 5 were tested and, as shown in Table 2, reactions
proceeded in satisfactory to good yields (50e78%) allowing a large
variety of polyfunctionalized anilines 6.
Table 1
Reaction optimization conditions
Promoter
Solvent
Reaction time
Yield %a
(h1þh2)
of 6aa
4.2.1. Ethyl 3-amino-4-cyano-2-ethyl-9H-fluorene-1-carboxy-
late. Compound 6aa brown solid, mp 123e125 ꢀC; [C19H18N2O2
Mw: 306.36; found: C, 74.55; H, 5.96; N, 9.11; requires C, 74.49; H,
5.92; N, 9.14%]; nmax (Nujol) 3474, 3362, 2924, 2216, 1707, 1621,
KF/Al2O3
Amberlyst A 21
TMG
First step: Amberlyst A 21
Second step: KF/Al2O3
TMG/SiO2
EtOAc
EtOAc
EtOAc
EtOAc
3þ25
3þ21
1þ1.5
3þ2
36
23
15
43
1462, 1377, 1220 cmꢁ1
; dH (400 MHz CDC13) 8.32 (1H, d, J 7.7 Hz),
7.52 (1H, d, J 7.3 Hz), 7.45e7.33 (2H, m), 4.60 (2H, br s), 4.47 (2H, q, J
14.5, 7.3 Hz), 3.82 (2H, s), 2.65 (2H, q, J 15.4, 7.7 Hz), 1.45 (3H, t, J
7.3 Hz), 1.26 (3H, t, J 7.7 Hz); dC (100 MHz, CDCl3) 168.3, 147.8, 144.4,
141.5, 139.0, 134.6, 131.6, 128.3, 127.3, 124.5, 124.4, 121.8, 117.2, 90.7,
61.8, 36.1, 22.7, 14.6, 13.2; m/z (EI, 70 eV) 306 (100, Mþ), 277 (65),
260 (56), 233 (37), 205 (25), 177 (10), 151 (7), 102 (4%).
EtOAc
MeCN
MeCN
Toluene
d
Traces
18
35
43
Traces
70
DBU
3þ48
4þ18
2.5þ8
d
Amberlyst A 21
Amberlyst A 21
CTAOH (10% water solution)
Et3N (1 equiv)
MeCN
4þ18
a
Yield of pure isolated product.
4.2.2. Ethyl 3-amino-4-cyano-2-(5-methoxy-5-oxopentyl)-9H-fluo-
rene-1-carboxylate. Compound 6ab yellow solid, mp 90e93 ꢀC;
[C23H24N2O4 Mw: 392.45; found: C, 70.43; H, 6.19; N, 7.12; requires
C, 70.39; H, 6.16; N, 7.14%]; nmax (Nujol) 3468, 3374, 2939, 2213,
It is important to note that byour procedure is possible to prepare an
uncommon class of penta-substituted anilines with the presence of
a cyano group in the o’-position, an ester functionality in the m-position
and an alkyl group in the o-position (the nature of the latter can be
1739, 1714, 1570, 1463, 1376, 1236 cmꢁ1
; dH (400 MHz CDC13) 8.30
modulated by the right choice of the starting b-nitroacrylates 5). The
(1H, d, J 7.3 Hz), 7.50 (1H, d, J 6.8 Hz), 7.43e7.31 (2H, m), 4.50 (2H, br
s), 4.46 (2H, q, J 14.1, 6.8 Hz), 3.80 (2H, s), 3.68 (3H, s), 2.66e2.60
(2H, m), 2.39 (2H, t, J 6.8 Hz), 1.80e1.71 (2H, m), 1.70e1.58 (2H, m),
1.44 (3H, t, J 6.8 Hz); dC (100 MHz, CDCl3) 174.2, 168.2, 148.0, 144.4,
141.6, 139.0, 134.6, 131.5, 128.3, 127.3, 124.9, 122.8, 121.7, 117.2, 90.7,
61.8, 51.9, 36.2, 33.6, 28.9, 27.7, 25.1, 14.6; m/z (EI, 70 eV) 392 (37,
Mþ), 346 (17), 319 (5), 291 (13), 263 (100), 258 (57), 244 (23), 218
(19), 190 (17), 165 (5%).
method works well with hindered and/or functionalized starting ma-
terials allowing the formation of a large variety of penta-substituted,
densely functionalized anilines (6ab, 6ad, 6ef, 6eh), including the
polycyclic ones (6aa,6ab,6ac,6ad). Inaddition, followingourprocedure,
even the presence of a stereogenic center can be preserved (6eh).
3. Conclusions
Thus, our procedure significantly enlarges the panorama of the
applicability of nitroalkenes in the productions of anilines. In fact,
as reported in Scheme 3: (i) from mono-substituted nitroalkenes5 it
4.2.3. Ethyl 3-amino-4-cyano-2-methyl-9H-fluorene-1-
carboxylate. Compound 6ac brown solid, mp 172e175 ꢀC;

S. Gabrielli et al. / Tetrahedron 68 (2012) 8231e8235
8233
Table 2
Anilines 3 obtained
Ylidene malonitrile 4
b
-nitroacrylate 5
Reaction (h1þh2)
4þ18
Aniline 6
Yield (%)a
NH2
COOEt
NC CN
NO2
COOEt
NC
NC
4a
4a
4a
4a
5a
5b
5c
2d
6aa
6ab
6ac
6ad
70
73
70
63
NH2
NC CN
NC CN
NC CN
NO2
NC
COOMe
MeOOC
4þ18
3þ18
6þ18
4
COOEt
NH2
COOEt
NO2
COOEt
COOEt
NO2
NH2
NC
COOMe
MeOOC
COOEt
COOEt
NH2
COOEt
NH2
NC CN
NC CN
NC CN
NO2
NC
NC
4b
4b
4c
5e
5f
3þ15
6þ18
6þ14
6be
6bf
6ca
63
56
62
3
4
COOEt
NO2
7
8
COOEt
COOEt
NH2
COOEt
NO2
COOEt
NC
5a
NH2
COOMe
NC CN
NC CN
NO2
COOMe
NC
4c
4d
4e
5g
5e
5f
6þ16
3þ48
6þ14
6cg
6de
6ef
50
50
67
NH2
NC
NO2
3
COOEt
4
COOEt
NH2
NC CN
NC
NO2
7
COOEt
8
COOEt
MeO
MeO
(continued on next page)

8234
S. Gabrielli et al. / Tetrahedron 68 (2012) 8231e8235
Table 2 (continued )
Ylidene malonitrile 4
b
-nitroacrylate 5
Reaction (h1þh2)
Aniline 6
Yield (%)a
NO2
NC CN
NH2
NC
4
O
4e
5h
6þ24
6eh
78
O
O
MeO
MeO
O
NH2
COOEt
NC CN
NC
NO2
4f
5i
24þ48
6fi
68
COOEt
a
Yield of pure, isolated product.
2.43e2.29 (2H, m), 1.84e1.67 (4H, m), 1.57e1.46 (2H, m), 1.41e1.28
(10H, m), 0.89 (3H, t, J 7.3 Hz); dC (100 MHz, CDCl3) 169.5, 146.7,
144.2, 139.5, 122.2, 121.5, 117.3, 97.8, 61.6, 32.4, 31.7, 29.4, 29.2, 28.3,
25.8, 22.6, 22.2, 17.4, 14.5, 14.2; m/z (EI, 70 eV) 328 (100, Mþ), 299
(28), 283 (19), 243 (65), 225 (13), 198 (28), 169 (18), 115 (5%).
NH2
ref. 5
ref. 6
NO2
R2
R2
(eq. 1)
NO2
7
NC CN
NH2 Ar1
O
NO2
Ar1
4.2.6. Ethyl 3-amino-4-cyano-5-methyl-2-nonyl-5,6,7,8-
(eq. 2)
(eq. 3)
R1
O
tetrahydronaphthalene-1-carboxylate. Compound
6bf
yellow
Ar
8
waxy; [C24H36N2O2 Mw: 384.55; found: C, 75.01; H, 9.49; N, 7.24;
requires C, 74.96; H, 9.44; N, 7.28%]; nmax (Nujol) 3459, 3368, 2912,
NH2
R
our
NO2
2211, 1716, 1645, 1215 cmꢁ1
; dH (400 MHz CDC13) 4.34e4.31 (4H,
procedure
R
m), 3.21e3.07 (1H, m), 2.54e2.48 (2H, m), 2.42e2.33 (2H, m),
1.85e1.67 (4H, m), 1.56e1.47 (2H, m), 1.38 (3H, t, J 6.8 Hz), 1.34e1.19
(15H, m), 0.87 (3H, t, J 7.3 Hz); dC (100 MHz, CDCl3) 169.6, 146.6,
144.2, 139.5, 122.3, 121.5, 117.3, 97.8, 61.5, 32.1, 31.7, 30.3, 29.7, 29.6,
29.5, 29.4, 29.2, 28.7, 25.8, 22.9, 22.3, 17.4, 14.5, 14.3; m/z (EI, 70 eV)
384 (100, Mþ), 355 (16), 271 (8), 243 (53), 198 (19), 169 (10%).
COOR1
COOR1
9
Scheme 3. New panorama of available anilines from nitroalkenes.
[C18H16N2O2 Mw: 292.33; found: C, 73.99; H, 5.55; N, 9.54; requires C,
73.95; H, 5.52; N, 9.58%]; nmax (Nujol) 3475, 3387, 2932, 2202, 1716,
4.2.7. Ethyl 5-amino-6-cyano-4-ethyl-2-methylbiphenyl-3-
carboxylate. Compound 6ca pale orange solid, mp 118e120 ꢀC;
[C19H20N2O2 Mw: 308.37; found: C, 74.09; H, 6.59; N, 9.03; requires
C, 74.00; H, 6.54; N, 9.08%]; nmax (Nujol) 3471, 3382, 2930, 2210,
1633, 1459, 1377, 1221 cmꢁ1
; dH (400 MHz CDC13) 8.29 (1H, d, J
7.7 Hz), 7.50 (1H, d, J 7.3 Hz), 7.43e7.32 (2H, m), 4.46 (2H, q, J 14.1,
7.3 Hz), 4.37 (2H, br s), 3.79 (2H, s), 2.23 (3H, s),1.45 (3H, t, J 7.3 Hz); dC
(100 MHz, CDCl3) 168.1, 148.3, 144.4, 141.2, 139.0, 134.5, 131.6, 128.2,
127.3,125.0,121.7,119.0,117.1, 90.3, 61.7, 36.2,14.8,14.6;m/z (EI, 70 eV)
292 (75, Mþ), 263 (100), 245 (18), 219 (57),190 (28),165 (10), 96 (8%).
1724, 1625, 1459, 1224 cmꢁ1
; dH (400 MHz CDC13) 7.48e7.37 (3H,
m), 7.25 (2H, d, J 7.7 Hz), 4.48 (2H, br s), 4.42 (2H, q, J 14.1, 7.3 Hz),
2.51 (2H, q, J 15.0, 7.3 Hz), 1.94 (3H, s), 1.40 (3H, t, J 6.8 Hz), 1.23 (3H,
t, J 7.3 Hz); dC (100 MHz, CDCl3) 169.6, 146.0, 143.7, 139.8, 138.2,
129.3,128.8,128.5,123.8,121.7,117.3, 98.9, 61.8, 22.8,16.3,14.5,13.0;
m/z (EI, 70 eV) 308 (100, Mþ), 279 (10), 265 (33), 233 (41), 219 (18),
205 (18), 190 (10), 165 (7%).
4.2.4. Ethyl 3-amino-4-cyano-2-(3-methoxy-3-oxopropyl)-9H-fluo-
rene-1-carboxylate. Compound 6ad yellow solid, mp 152e154 ꢀC;
[C21H20N2O4 Mw: 364.39; found: C, 69.29; H, 5.57; N, 7.64; requires
C, 69.22; H, 5.53; N, 7.69%]; nmax (Nujol) 3461, 3365, 2924, 2221,
1738, 1719, 1651, 1230 cmꢁ1
; dH (400 MHz CDC13) 8.32 (1H, d, J
4.2.8. Methyl 5-amino-6-cyano-4-ethyl-2-methylbiphenyl-3-
carboxylate. Compound 6cg pale orange solid, mp 158e162 ꢀC;
[C18H18N2O2 Mw: 294.35; found: C, 73.51; H, 6.20; N, 9.48; requires
C, 73.45; H, 6.16; N, 9.52%]; nmax (Nujol) 3452, 3371, 2210, 1723,
7.7 Hz), 7.51 (1H, d, J 7.7 Hz), 7.44e7.33 (2H, m), 4.97 (2H, br s), 4.47
(2H, q, J 14.5, 7.7 Hz), 3.82 (2H, s), 3.71 (3H, s), 2.98 (2H, t, J 7.3 Hz),
2.71 (2H, t, J 7.3 Hz), 1.45 (3H, t, J 7.7 Hz); dC (100 MHz, CDCl3) 174.4,
168.0, 148.4, 144.5, 142.3, 138.8, 134.7, 131.8, 128.5, 127.4, 125.0,
121.9, 121.7, 117.1, 91.2, 61.9, 52.3, 36.4, 33.5, 24.2, 14.6; m/z (EI,
70 eV) 364 (54, Mþ), 332 (17), 290 (29), 276 (68), 259 (100), 229
(29), 205 (23), 190 (20), 177 (9%).
1650, 1456, 1229 cmꢁ1
; dH (400 MHz CDC13) 7.47e7.38 (3H, m),
7.26e7.22 (2H, m), 4.48 (2H, br s), 3.93 (3H, s), 2.48 (2H, q, J 15.4,
7.3 Hz), 1.92 (3H, s), 1.22 (3H, t, J 7.7 Hz); dC (100 MHz, CDCl3) 170.1,
146.0, 143.6, 139.7, 138.2, 129.3, 129.0, 128.5, 124.0, 121.8, 117.2, 99.0,
52.6, 23.0, 16.8, 13.0; m/z (EI, 70 eV) 294 (100, Mþ), 279 (61), 263
(19), 233 (35), 219 (23), 205 (20), 165 (6%).
4.2.5. Ethyl 3-amino-4-cyano-5-methyl-2-pentyl-5,6,7,8-tetrahy-
dronaphthalene-1-carboxylate. Compound 6be yellow waxy;
[C20H28N2O2 Mw: 328.45; found: C, 73.20; H, 8.65; N, 8.48; requires
C, 73.14; H, 8.59; N, 8.53%]; nmax (Nujol) 3479, 3383, 2936, 2209,
4.2.9. Ethyl 3-amino-4-cyano-5,6-diphenyl-2-pentylbenzoate. Compound
6de brown solid, mp 150e153 ꢀC; [C27H28N2O2 Mw: 412.52; found:
C, 78.68; H, 6.87; N, 6.73; requires C, 78.61; H, 6.84; N, 6.79%]; nmax
1732, 1634, 1456, 1218 cmꢁ1
;
dH (400 MHz CDC13) 4.37 (2H, q, J 14.1,
(Nujol) 3454, 3366, 2923, 2213,1716,1456,1225 cmꢁ1
; dH (400 MHz
7.7 Hz), 4.22 (2H, br s), 3.20e3.11 (1H, m), 2.54e2.48 (2H, m),

S. Gabrielli et al. / Tetrahedron 68 (2012) 8231e8235
8235
CDC13) 7.22e7.16 (3H, m), 7.12e7.05 (5H, m), 7.00e6.95 (2H, m),
4.64 (2H, br s), 3.94 (2H, q, J 14.1, 6.8 Hz), 2.56e2.50 (2H, m),
1.72e1.58 (2H, m), 1.44e1.32 (4H, m), 0.93 (3H, t, J 6.8 Hz), 0.89 (3H,
t, J 6.8 Hz); dC (100 MHz, CDCl3) 168.8, 147.6, 143.1, 139.9, 137.8,
137.6, 130.8, 130.2, 128.9, 128.1, 128.0, 127.7, 127.1, 122.9, 117.3, 98.6,
61.5, 32.4, 29.6, 28.3, 22.7, 14.2, 13.8; m/z (EI, 70 eV) 412 (100, Mþ),
367 (10), 327 (60), 309 (23), 281 (13), 254 (9%).
(2H, br s), 2.96e2.86 (2H, m), 2.75e2.67 (2H, m), 2.48e2.35 (1H, m),
1.43 (3H, t, J 7.3 Hz), 1.68e1.10 (8H, m), 1.06e0.79 (2H, m); dC
(100 MHz, CDCl3) 170.1, 145.7, 144.5, 141.4, 139.1, 131.5, 129.5, 129.0,
128.5, 128.4, 128.3, 126.8, 122.2, 117.0, 69.1, 61.8, 43.7, 34.8, 32.9,
31.9, 27.6, 26.2, 26.1, 14.5; m/z (EI, 70 eV) 452 (100, Mþ), 407 (9), 361
(84), 333 (60), 263 (35), 219 (41), 105 (25), 91 (26%).
Acknowledgements
4.2.10. Ethyl 5-amino-6-cyano-40-methoxy-4-nonyl-2-propylbi-
phenyl-3-carboxylate. Compound 6ef pale yellow solid, mp
93e95 ꢀC; [C29H40N2O3 Mw: 464.64; found: C, 75.02; H, 8.71; N,
5.99; requires C, 74.96; H, 8.68; N, 6.03%]; nmax (Nujol) 3458, 3366,
We gratefully acknowledge financial support from the MIUR
Italy (FIRB National Projects ‘Metodologie di nuova generazione
nella formazione di legami carbonioecarbonio
ioeeteroatomo in condizioni eco-sostenibili’ and ’Metodologie di
sintesi innovative e sostenibili per processi di attivazione del
legame CeH0). We also wish to thank the Universities of Camerino
and Perugia for financial support.
e
carbon-
2924, 2216, 1720, 1610, 1463, 1214 cmꢁ1
; dH (400 MHz CDC13) 7.18
(2H, d, J 8.9 Hz), 6.96 (2H, d, J 8.5 Hz), 4.43 (2H, br s), 4.40 (2H, q, J
14.5, 7.3 Hz), 3.85 (3H, s), 2.46e2.39 (2H, m), 2.28e2.21 (2H, m),
1.63e1.54 (2H, m), 1.40 (3H, t, J 7.3 Hz), 1.34e1.22 (14H, m), 0.88
(3H, t, J 7.3 Hz), 0.67 (3H, t, J 7.7 Hz); dC (100 MHz, CDCl3) 169.6,
159.6, 146.0, 143.6, 139.7, 130.5, 130.4, 127.5, 122.8, 117.4, 114.0, 99.7,
61.6, 55.4, 32.9, 32.1, 30.3, 29.8, 29.7, 29.6, 29.5, 24.8, 22.9, 14.6, 14.5,
14.4; m/z (EI, 70 eV) 464 (100, Mþ), 435 (55), 419 (10), 362 (10), 232
(19), 293 (15), 263 (19), 249 (32), 206 (8%).
References and notes
1. Ballini, R.; Marcantoni, E.; Petrini, M. In Amino Group Chemistry; Ricci, A., Ed.;
Wiley-VCH: Weinheim, 2008; pp 93e144.
2. Ballini, R.; Gabrielli, S.; Palmieri, A.; Petrini, M. Curr. Org. Chem. 2001, 15,
1482e1506.
3. The Chemistry of Anilines; Rappoport, Z., Ed.; John Wiley and Sons: Jerusalem,
2007; pp 455e536.
4. Ballini, R.; Barboni, L.; Femoni, C.; Giarlo, G.; Palmieri, A. Tetrahedron Lett. 2006,
47, 2295e2297 and references cited therein.
5. Xue, D.; Zhang, Z.-L.; Deng, J.-G. J. Org. Chem. 2007, 72, 5443e5445.
6. Li, P.; Luo, L.-L.; Li, X.-S.; Xie, J.-J. Tetrahedron 2010, 66, 7590e7594.
7. Alfonsi, K.; Colberg, J.; Dunn, P. J.; Fevig, T.; Jennings, S.; Johonson, T. A.; Kleine,
H. P.; Knight, C.; Nagy, M. A.; Perry, D. A.; Stefaniak, M. Green Chem. 2008, 10,
31e36.
4.2.11. (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 5-amino-6-cyano-
40-methoxy-4-pentyl-2-propylbiphenyl-3-carboxylate. Compound
6eh yellow solid, mp 42e45 ꢀC; [C33H46N2O3 Mw: 518.73; found: C,
20
76.48; H, 9.00; N, 5.37; requires C, 76.41; H, 8.94; N, 5.40%]; [a]
D
ꢁ32.5 (c 0.1, CHCl3); nmax (Nujol) 3478, 3382, 2922, 2213, 1725, 1611,
1456, 1213 cmꢁ1
dH (400 MHz CDC13) 7.18 (2H, d, J 7.7 Hz), 6.96
;
(2H, d, J 8.5 Hz), 4.98 (1H, td, J 15.0, 10.7, 4.2 Hz), 4.41 (2H, br s), 3.85
(3H, s), 2.51e2.37 (2H, m), 2.35e2.13 (3H, m), 1.97e1.88 (1H, m),
1.77e1.70 (2H, m), 1.63e1.19 (11H, m), 1.14e1.03 (2H, m), 0.96e0.89
(9H, m), 0.83 (3H, t, J 7.3 Hz), 0.65 (3H, t, J 7.3 Hz); dC (100 MHz,
CDCl3) 169.4, 159.5, 146.0, 143.7, 140.0, 130.6, 130.4, 127.4, 122.6,
117.3, 114.1, 114.0, 99.7, 76.5, 55.4, 46.9, 40.9, 34.3, 39.9, 32.6, 31.7,
29.8, 28.4, 25.9, 24.9, 22.9, 22.8, 22.3, 21.1, 15.9, 14.4, 14.3; m/z (EI,
70 eV) 518 (66, Mþ), 379 (76), 351 (100), 323 (15), 281 (26), 249
(24), 83 (33), 55 (33%).
8. (a) Ballini, R.; Fiorini, D.; Palmieri, A. Tetrahedron Lett. 2004, 45, 7027e7029; (b)
Ballini, R.; Fiorini, D.; Palmieri, A. Tetrahedron Lett. 2005, 46, 1245e1246; (c)
Ballini, R.; Gabrielli, S.; Palmieri, A.; Petrini, M. Tetrahedron 2008, 64,
ꢀ
5435e5441; (d) Ballini, R.; Bazan, N. A.; Bosica, G.; Palmieri, A. Tetrahedron Lett.
2008, 49, 3865e3867; (e) Ballini, R.; Bosica, G.; Palmieri, A.; Bakhtiari, K. Synlett
2009, 268e270; (f) Ballini, R.; Bosica, G.; Gabrielli, S.; Palmieri, A. Tetrahedron
2009, 65, 2916e2920; (g) Ballini, R.; Gabrielli, S.; Palmieri, A. Synlett 2009,
965e967; (h) Ballini, R.; Palmieri, A.; Talaq, M. A.-K.; Gabrielli, S. Adv. Synth.
Catal. 2009, 351, 2611e2614; (i) Palmieri, A.; Gabrielli, S.; Ballini, R. Adv. Synth.
Catal. 2010, 352, 1485e1492; (j) Ballini, R.; Gabrielli, S.; Palmieri, A. Synlett 2010,
2468e2470; (k) Palmieri, A.; Ley, S. V.; Polyzos, A.; Ladlow, M.; Baxendale, I. R.
Beilstein J. Org. Chem. 2009, 5, No. 23; (l) Ishikawa, H.; Suzuki, T.; Hayashi, Y.
Angew. Chem., Int. Ed. 2009, 48, 1304e1307; (m) Ishikawa, H.; Suzuki, T.; Orita,
H.; Uchimaru, T.; Hayashi, Y. Chem.eEur. J. 2010, 16, 12616e12626; (n) Palmieri,
A.; Gabrielli, S.; Lanari, D.; Vaccaro, L.; Ballini, R. Adv. Synth. Catal. 2011, 353,
1425e1428; (o) Palmieri, A.; Gabrielli, S.; Cimarelli, C.; Ballini, R. Green Chem.
2011, 13, 3333e3336.
4.2.12. Ethyl 5-amino-6-cyano-2-cyclohexyl-4-phenethylbiphenyl-3-
carboxylate. Compound 6fi orange solid, mp 52e55 ꢀC;
[C30H32N2O2 Mw: 452.59; found: C, 76.98; H, 7.36; N, 6.14; requires
C, 79.61; H, 7.31; N, 6.19%]; nmax (Nujol) 3474, 3378, 2910, 2213,1731,
1627, 1461, 1210 cmꢁ1
;
dH (400 MHz CDC13) 7.48e7.42 (3H, m),
9. Chen, K. D.; Cui, Y. C.; Wang, X.; Zhu, Q. W.; Deng, J. G. J. Org. Chem. 2005, 70,
7.38e7.31 (2H, m), 7.29e7.21 (5H, m), 4.45 (2H, q, J 14.1, 7.3 Hz), 4.36
3584e3591.