Reactions of 1-nitrocyclohexene with alicyclic amines

Article abstract of DOI:10.1134/S107036321309020X

The interaction of 1-nitrocyclohexene with alicyclic amines can proceed via nucleophilic addition at the carbon-carbon double bond (morpholine, piperazine) to form aza-Michael products or as deprotonation (piperidine, azepane) to give ammonium salts, 2-cyclohexene-1-nitronates. The preferred reaction pathway is determined by the amine basicity.

Full text of DOI:10.1134/S107036321309020X

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 9, pp. 1751–1754. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © I.E. Efremova, L.V. Lapshina, M.I. Vakulenko, V.M. Berestovitskaya, 2013, published in Zhurnal Obshchei Khimii, 2013, Vol. 83,
No. 9, pp. 1534–1537.
On the 100th anniversary of V.V. Perekalin
Reactions of 1-Nitrocyclohexene with Alicyclic Amines
I. E. Efremova, L. V. Lapshina, M. I. Vakulenko, and V. M. Berestovitskaya
Herzen State Pedagogical University of Russia, Moyka emb. 48, St. Petersburg, 191186 Russia
e-mail: kohrgpu@yandex.ru
Received February 7, 2013
Abstract—The interaction of 1-nitrocyclohexene with alicyclic amines can proceed via nucleophilic addition
at the carbon–carbon double bond (morpholine, piperazine) to form aza-Michael products or as deprotonation
(piperidine, azepane) to give ammonium salts, 2-cyclohexene-1-nitronates. The preferred reaction pathway is
determined by the amine basicity.
DOI: 10.1134/S107036321309020X
Reactions involving N-nucleophiles form an important
part of the unsaturated nitro compounds chemistry [1, 2],
however, understanding of their products in the case of
carbocyclic nitroalkenes is not straightforward. For
example, the interaction of 1-nitrocyclohexene with
substituted pyrrolidine and piperidine may result in the
products of nucleophilic addition or salt formation [3].
According to the authors of [3], the reaction pathway is
determined by spatial structure of the nucleophile.
For example, the reactions with morpholine (рKа
HB+ 8.97) and piperazine (рKа HB+ 9.90) occurred
within 24 h to give the products of mono-addition (II)
and bis-addition (III).
In the reaction of nitroalkene I with the more basic
piperidine and azepane (рKа or HB+ was 11.12 and
11.24, respectively) the CH-acidic properties of С3Н2
methylene group of nitrocyclohexene were more
pronounced. The reaction resulted in ammonium 2-
cyclohexene-1-nitronates IV and V, easily isolated by
treating the reaction mixture with diethyl ether.
We investigated the interaction of 1-nitrocyclo-
hexene I with some sterically similar secondary ali-
cyclic amines of different basicity (рKа of HB+ values
were taken from [7]). The experiments performed at
room temperature in bulk proved that the amine
basicity determined the preferred reaction pathway:
either nucleophilic addition or deprotonation of the
carbocycle allyl methylene group.
Obtained compounds II–V were stable crystalline
1
substances; their structure was elucidated by H NMR,
1
13C NMR, H–13C HMQC, IR, and UV spectroscopy
methods. The structurally similar salts of nitro-
cyclohexene obtained in [3] were not characterized and
described as individual substances.
−O2N
O2N
NO2
HN
O
HN
2
n
6
4
1
5
1
3
+NH2
IV, V
3
2
6
5
N
O
n
4
I
II
HN
NH
O2N
NO2
6
4
6
4
1
3
1
2
2
5
5
N
N
3
III
n = 1 (IV), 2 (V).
1751

1752
EFREMOVA et al.
δ, ppm
1Н–13С HMQC NMR spectrum of V in DMSO-d6.
In the IR spectra of aminonitrocyclohexanes II and
1H and 13C NMR spectra were important to confirm
the structures of IV and V. The 1H NMR spectra of IV
and V contained the signals of olefinic protons С3Н
(multiplet, 5.41–5.44 ppm) and of С2Н (doublet, 6.60–
6.62 ppm), along with the signals assigned to
methylene groups protons of heterocyclic ammonium
cation and to carbocyclic anion.
The 13C NMR spectra of IV and V contained the
downfield signals of sp2 carbon atoms (С1, C2, and С3)
of cyclohexene nitronate anion in the range of 117.37–
123.88 ppm; they were assigned on the basis of 1Н–13С
HMQC data. For example, the absence of any cross-
peaks of the 117.55 ppm signal in the spectrum of V
allowed its assignment to С1 (see figure). Then, the
correlation of the signals at 123.07 and 123.43 ppm
with the signals of olefinic protons (multiplet of С3Н
and doublet of С2Н) allowed their assignment to C3
and C2, respectively.
III, the absorption bands of non-conjugated nitro
group (1550–1553, 1377–1378 cm–1) were observed.
1
In the H NMR spectra of those adducts the proton
signals of all structural fragments were identified. The
signals of methylene protons of the cyclohexane ring
and those of heterocyclic amines appeared as strongly
coupled multispin systems in the range of 1.20–
3.45 ppm. The spectra contained complex multiplets of
nitromethine (4.56–4.72 ppm) and aminomethine
(2.76–2.84 ppm) protons as well. The chemical shifts
of those groups were close to those of the known
vicinal aminonitrocyclohexanes [4, 6].
Parameters of the nitronates IV and V electronic
spectra (absorption maximum at 285–287 nm, ε =
12300–14200) were close to those reported in the
literature for the corresponding nitrocyclohexene salts
(λmax = 278 nm, ε = 16100, [8]). The IR spectra of
those compounds contained vibrational bands of the
ionized nitro group (1354, 1216–1221, 1154–1160,
and 1063–1064 cm–1), of С=С and С=N+ double bonds
(1624–1626, 1551–1596, and 1534–1537 cm–1), and of
the ammonium groups N–H bonds (2318–2736 cm–1).
To conclude, the study of model reactions with
alicyclic amines demonstrated that the pathway of 1-
nitrocyclohexene I interaction depended on the
nucleophilic reagent basicity: the aza-Michael adducts
were formed in the case of amines with рKа(HB+) less
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1753
REACTIONS OF 1-NITROCYCLOHEXENE WITH ALICYCLIC AMINES
than 11.12 (morpholine, piperazine). When more basic
reagents were used, the nitrocyclohexene system was
acting as a CH-acid to give corresponding conjugated
2-cyclohexene-1-nitronates.
δН, ppm: 1.20–1.29 m, 1.67–1.79 m (6Н, С3Н2, С4Н2,
С5Н2), 1.82–2.05 m (2Н, С6Н2), 2.29–2.62 m (4Н,
СН2N), 3.36–3.49 m (4Н, СН2O), 2.78–2.85 m (1Н,
С2Н), 4.68–4.75 m (1Н, С1Н). 13С NMR spectrum, δC,
ppm: 86.77 (C1), 66.07 (C2), 24.56, 22.67, 23.82, 31.56
(C3, C4, C5, C6), 48.85 (2С, СH2N), 67.19 (2С, СH2O).
Found N, %: 12.97. C10H18N2O3. Calculated N, %:
13.07.
EXPERIMENTAL
The 1H, 13C–{1H}, and 1H–13C HMQC NMR
spectra were recorded with Jeol ECX400A spectro-
meter [399.78 (1H), 100.525 (13C) MHz] in DMSO-d6,
the residual non-deuterated solvent signals were used
as internal reference. The IR spectra were registered
with Shimadzu IRPrestige-21 Fourier spectrometer in
KBr pellets. The electronic absorption spectra were
recorded with Shimadzu UV2401PC spectrophotometer
in quartz cuvettes (l = 0.1 cm, c = 1.0×10–3 mol l–1 in
ethanol). Elemental analysis was performed with Euro-
vector EA 3000 (CHN Dual mode) analyzer.
1,4-Bis(2-nitrocyclohexyl)piperazine (III). 0.32 g
(4 mmol) of piperazine was added to 1.00 g (8 mmol)
of 1-nitrocyclohexene I. After 24 h incubation, the
resulting precipitate was filtered off and washed with
cold diethyl ether. Yield 0.29 g (22%), mp 153–155ºC.
1
IR spectrum (KBr), ν, cm–1: 1550, 1373 (NO2). Н
NMR spectrum, δН, ppm: 1.21–1.29 m, 1.69–1.82 m
and 2.05–2.25 m (16Н, С3Н2, С4Н2, С5Н2, С6Н2),
2.59–2.61 m (8Н, СН2N), 2.76–2.84 m (2Н, С2Н),
4.56–4.65 m (2Н, С1Н). Found N, %: 16.54.
C16H28N4O4. Calculated N, %: 16.46.
1-Nitrocyclohexene (I) was synthesized by nitro-
mercurization method [9], which was modified to
avoid direct contact with the highly toxic reagent, mer-
cury(II) chloride. A suspension of 40.00 g (180 mmol)
of mercury(II) oxide in 20 ml of distilled water was
added to 150 ml of 10% hydrochloric acid (d =
1.05 g cm–3). After 5 min, 25.20 g (360 mmol) of
sodium nitrite and 14.76 g (18.22 ml, 180 mmol) of
cyclohexene were added to the mixture. The resulting
mixture was incubated for 72 h at room temperature.
(2-Nitrocyclohexyl)mercury chloride was filtered off
(37.59 g, 110 mmol, 61%), dissolved in 200 ml of
dichloromethane, and mixed with 44 ml of 2.5 M
sodium hydroxide solution (110 mmol). The reaction
mixture was stirred for 5 min, and then 40.15 ml of
10% hydrochloric acid (110 mmol) was added. The
inorganic residue was filtered off; the mother liquor
was separated in a separating funnel. The organic layer
was dried over anhydrous magnesium sulfate and then
concentrated under reduced pressure. The residue was
distilled in vacuum. Yield 10.83 g (47%), pale yellow
oil, bp 72–74°С (4 mm Hg), nD20 1.5052 {bp 71.5°С
(3 mm Hg), nD20 1.5051 [10]}. Inorganic residue con-
taining mercury and soluble salts (NaCl, HgCl2) was
treated with diluted nitric acid.
Piperidinium 2-cyclohexene-1-nitronate (IV).
0.34 g (0.39 ml, 4 mmol) of piperidine was added to
0.50 g (4 mmol) of 1-nitrocyclohexene I. After 24 h of
incubation, the reaction mixture was treated with 2 ml
of anhydrous ether. The resulting precipitate was
filtered off, washed with cold diethyl ether, and dried
in air. Yield 0.77 g (91%), mp 68–70ºC. IR spectrum
-
(KBr), ν, cm–1: 1354, 1221, 1154, 1063 (NO2 ), 1626,
+
1551, 1537 (C=C, C=N+), 2318–2736 (NH2 ). UV
spectrum, λmax, nm (ε): 287 (12300). 1Н NMR
spectrum, δН, ppm: 1.51–1.53 m, 1.61–1.64 m and
2.82–2.84 m [10Н, (СН2)5], 1.55–1.60 m, 1.96–2.00
m, 2.40–2.44 m (6Н, С4Н2, С5Н2, С6Н2), 5.41–5.64 m
(1Н, С1Н), 6.60 d (1Н, С2Н, J 10.4 Hz). 13С NMR
spectrum, δC, ppm: 122.85 (C3), 123.88 (C2), 117.37
(C1), 22.30, 25.56, 25.00, 24.72 [6С, C4, C5, C6, (СH2)3],
44.23 (2С, СH2N). Found N, %: 13.48. C11H20N2O2.
Calculated N, %: 13.20.
Azepanium 2-cyclohexene-1-nitronate (V) was
prepared similarly. Yield 50%, mp 49–50ºC. IR spec-
trum (KBr), ν, cm–1: 1354, 1216, 1160, 1064 (NO2–),
1624, 1596, 1534 (C=C, C=N+), 2396–2727 (NH2+).
1
UV spectrum, λmax, nm (ε): 285 (14200). Н NMR
spectrum, δН, ppm: 1.50–1.52 m, 1.63–1.67 m, 2.89–
2.92 m [12Н, (СН2)6], 1.55–1.58 m, 1.94–1.96 m,
2.40–2.43 m (6Н, С4Н2, С5Н2, С6Н2), 5.40–5.42 m
(1Н, С1Н), 6.62 d (1Н, С2Н, J 10.1 Hz). 13С NMR
spectrum, δC, ppm: 123.07 (C3), 123.43 (C2), 117.55
(C1), 22.29, 25.56, 25.00, 26.95, 28.05 [7С, C4, C5, C6,
(СH2)4], 46.04 (2С, СH2N). Found N, %: 11.99.
C12H22N2O2. Calculated N, %: 12.38.
2-Morpholino-1-nitrocyclohexane (II). 0.35 g
(0.35 ml, 4 mmol) of morpholine was added to 0.50 g
(4 mmol) of 1-nitrocyclohexene I. After 24 h
incubation, the reaction mixture was treated with 2 ml
of anhydrous ether. The resulting precipitate was
filtered off, washed with cold diethyl ether, and dried
in air. Yield 0.64 g (75%), mp 62–64ºC. IR spectrum
1
(KBr), ν, cm–1: 1553, 1378 (NO2). Н NMR spectrum,
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EFREMOVA et al.
Bonne, D., and Rodriguez, J., Eur. J. Chem., 2009,
Physico-chemical studies were performed in the
Center for Collective Use in Herzen State Pedagogical
University of Russia.
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6. Vakulenko, M.I., Lapshina, L.V., Grishhenko, S.I.,
Efremova, I.E., and Berestovitskaya, V.M., Russ. J.
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