Unprecedented two-step synthesis of symmetrical diarylamines from 2-alkyl-1,3-dinitropropanes

Article abstract of DOI:10.1016/j.tetlet.2006.02.027

This letter reports a new, two-step synthesis of symmetrical diarylamines from 1,3-dinitropropanes, by their reaction with acrolein under basic conditions (Al2O3, neat), followed by aromatisation of the obtaines 2,4-dinitrocyclohexanols, through their tre

Full text of DOI:10.1016/j.tetlet.2006.02.027

Tetrahedron Letters 47 (2006) 2295–2297
Unprecedented two-step synthesis of symmetrical diarylamines
from 2-alkyl-1,3-dinitropropanes
a,
b
a
Roberto Ballini,a,* Luciano Barboni, Cristina Femoni, Guido Giarlo
*
and Alessandro Palmieria
a
`
Dipartimento di Scienze Chimiche dell’Universita di Camerino, Via S. Agostino 1, 63032 Camerino, Italy
`
Dipartimento Chimica Fisica e Inorganica, Universita di Bologna, Viale Risorgimento 4, 40136 Bologna, Italy
b
Received 12 January 2006; revised 2 February 2006; accepted 3 February 2006
Available online 21 February 2006
Abstract—This letter reports a new, two-step synthesis of symmetrical diarylamines from 1,3-dinitropropanes, by their reaction with
acrolein under basic conditions (Al2O3, neat), followed by aromatisation of the obtained 2,4-dinitrocyclohexanols, through their
treatment with four equivalents of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), in acetonitrile as a solvent, and warming overnight
at 60 °C.
Ó 2006 Elsevier Ltd. All rights reserved.
Arylamines are found in pharmaceuticals,1,2 materials
with important electronic properties,3–15 and ligands
for early metal catalysts.16 Despite the simplicity of the
arylamine moieties, the synthesis of these compounds
is often difficult.17 Procedures involving nitration, reduc-
tion or substitution are incompatible with many func-
tional groups and often comprise protection and
deprotection steps. Reductive amination, which impli-
cates formation of an imine from an arylamine and sub-
sequent reduction of the imine, needs two steps, a
preformed C–N bond in an aniline, an excess of the
amine, and sluggish reductions.18–21 On the other hand,
copper-mediated (Ullmann) substitutions demand high
temperatures,22–25 while direct nucleophilic substitution
of aryl halides typically requires a large excess of
reagent, high temperature or highly activated aryl
halides.26,27 Alternatively, transition metal–arene com-
plexes28 or palladium acetates (Buchwald–Hartwig pro-
cedure)29 have been employed, but stoichiometric
amounts of the metal complex are required or low chemo-
selectivity is observed. Anyway, all the above procedures
need the presence of a preformed aromatic system.
matic rings,30 and several methods are known for this
purpose.31 In this context, nitroalkane derivatives have
emerged, over the last years, as versatile precursors for
the synthesis of a variety of aromatic systems.32–34
During our efforts devoted to the use of nitroalkanes as
versatile precursors for the preparation of aromatic
structures,32,33 we have now discovered a new, two-step
synthesis of symmetrical diarylamines, starting from 1,3-
dinitropropanes.35
Thus, the reaction of 1,3-dinitroalkanes 1 with acrolein,
under basic conditions (basic Al2O3, neat) affords the
nitrocyclohexanols 2 in a one-pot sequence36 (Scheme
1), through tandem Michael/nitroaldol (Henry) reac-
tions. After extraction, treatment of the crude 2, with
4 equiv of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), in
acetonitrile as a solvent, and warming overnight at
60 °C, directly produces the diarylamines 3 in satisfac-
tory overall yields (32–45%, Table 1).
Some spectral features conducted us to the structure of
compounds 3: (i) the high molecular weights indicate
that two molecules of the starting material are included
in 3 and, since the molecular weights are odd, an odd
Aromatization of acyclic precursors is undoubtedly a
useful reaction in the synthesis of highly substituted aro-
1
number of N-atoms are present; (ii) H NMR spectra
indicate 3 as symmetric molecules and the presence of
one exchangeable proton around 5.5 ppm is compatible
with symmetric secondary amines. The 1H NMR spectra
also show the 1,2,3-substitution of the nitroaromatic
Keywords: Diarylamines; Aromatization; 1,3-Dinitropropanes; One-
pot synthesis.
*
Corresponding authors. Tel.: +39 0737402270; fax: +39
0737402297; e-mail: roberto.ballini@unicam.it
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.02.027

2296
R. Ballini et al. / Tetrahedron Letters 47 (2006) 2295–2297
It should be noted that the synthesis of substituted biphe-
R
nyls (compounds 3b,c) can also be accomplished.
O2N
HO
NO2
NO2
NO2
CHO
Al2O3
neat, r.t.
R
In conclusion, the simplicity of execution, the ready
availability of the substrates, the broad range of poten-
tial products, the avoidance of a workup, since the crude
mixture can be directly charged to a chromatographic
column for the immediate purification, make this syn-
thetic strategy very attractive for academic research
and practical applications. For the time being we are
aiming to verify the mechanism of the reaction and to
enlarge the potential of our discovery.
1
2
DBU (4 equiv.)
CH3CN, 60 C
˚
overnight, 32-45%
R
H
N
R
O2N
NO2
3a-j
Acknowledgements
Scheme 1.
The authors thank the University of Camerino and the
`
Ministero dell’Istruzione, dell’Universita e della Ricerca,
Italy, for financial support.
Table 1. Symmetrical diarylamines 3
Entry
R
Reaction time Yield (%)a
1 to 2 (h)
from 1
Supplementary data
a
b
c
d
e
f
g
h
i
Ph
4
5
18
6
5
9
5
5
6
6
42
36
37
36
35
32
36
38
36
45
p-CF3C6H4
p-MeOC6H4
PhCH2CH2
CH3(CH2)4CH@CH(CH2)2
i-Pr
Method of preparation and spectral data of compounds
3, X-ray structures of compounds 3b and 3j, X-ray data
collection procedure, and 13C NMR spectra of com-
pounds 3a–3j. Supplementary data associated with this
article can be found, in the online version, at
doi:10.1016/j.tetlet.2006.02.027.
n-Pr
CH3(CH2)4
CH3(CH2)7
c-C6H11
j
a Yields of pure, isolated compounds.
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