Synthesis and properties of the salts of 1-nitropropan-2-one and 1-nitrobutan-2-one

Article abstract of DOI:10.1016/j.mencom.2020.03.015

A new safe synthesis of α-nitro ketone salts via alkaline hydrolysis of 2-morpholino-1-nitroalkenes has been developed. The salts were introduced into the reactions of diazotization and heterocyclization. Crystal structures of new 2-morpholino-1-nitrobut-1-ene and 6-ethyl-5-nitro-4phenyl-3,4-dihydropyrimidin-2-one have been determined.

Full text of DOI:10.1016/j.mencom.2020.03.015

Mendeleev
Communications
Mendeleev Commun., 2020, 30, 177–179
Synthesis and properties of the salts
of 1-nitropropan-2-one and 1-nitrobutan-2-one
Vladimir L. Rusinov,a,b Roman A. Drokin,*a Dmitrii V. Tiufiakov,a
Egor K. Voinkova and Evgeny N. Ulomskya,b
a Institute of Chemical Engineering, Ural Federal University, 620002 Ekaterinburg, Russian Federation.
E-mail: drokinroman@gmail.com
b I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
620108 Ekaterinburg, Russian Federation
DOI: 10.1016/j.mencom.2020.03.015
O
O2N
A new safe synthesis of a-nitro ketone salts via alkaline
hydrolysis of 2-morpholino-1-nitroalkenes has been
developed. The salts were introduced into the reactions of
diazotization and heterocyclization. Crystal structures of
new 2-morpholino-1-nitrobut-1-ene and 6-ethyl-5-nitro-4-
phenyl-3,4-dihydropyrimidin-2-one have been determined.
PhN2+
R
O
R
N
N
O
O
N
O
PhHN
NaOH
EtOH
N
O
O
–
R
O
ArCHO,
urea
Na+
HN
NH
Ar
R
NO2
Keywords: nitro compounds, ketones, nitroazine systems, nitroacetone, enamines, diazonium salts, pyrimidinones, hydrazones.
a-Nitro ketones are highly reactive compounds with a wide
synthetic potential because they contain both nucleophilic and
electrophilic reaction centers. For the same reason, they are unstable
and difficult to prepare, which limits their use in organic synthesis.
Previously developed methods for the synthesis of a-nitro ketones
have significant disadvantages. Their preparation from imidazoles,
benzimidazoles or benzotriazoles acylated at the nitrogen atom
requires the use of an explosive nitromethane salt.1–3 The synthesis
of nitro ketones from 2-dimethylamino-1-nitroprop-1-ene4 or from
halo ketones5 typically results in low yields of the target products.
Nitration of acetylacetone followed by deacylation leads to
nitroacetone with a total yield of 15%.6 Oxidation of nitroprop-1-
ene proceeds with a 37% yield,7 whereas the preparation of
a-nitroacetone from dimethylbutadiene requires unstable toxic
nitrous anhydride and ozone, and the total yield for the two steps is
11%.8 High yields (up to 80%) of nitro ketones can be achieved
upon oxidation of nitro alcohols,9–12 however, free nitro ketones
themselves are generally unstable and can be unpredictably
destroyed in the course of isolation and storage.13
Thus, nitroacetone was converted into 4-indolyl-3-nitrobutan-2-
one,14 nitrophenylbutadienes,15 oxazoles,16,17 nitropyrroles and
their uncyclic precursors, enamines,18 dihydropyranes15 as well
as nitropyridines.19–21 1-Nitrobutan-2-one was used for the
synthesis of nitropyridines,22 aryl nitromethyl ketones,23
a-amino ketone hydrochlorides24 and N-hydroxy-2-oxoalkan-
imidothioates.1
Therefore, development of a simple, safe and effective method
for the synthesis of nitro ketones in their stable form seems an
urgent task for organic chemistry. In this work, a new efficient
synthesis of stable salts of 1-nitroacetone and 1-nitrobutan-2-one
has been proposed, and the possibility of their application in the
reactions known for free nitro ketones has been proved.
As precursors of a-nitro ketones, we used readily available
2-morpholino-1-nitroprop-1-ene 1a and 2-morpholino-1-nitro-
but-1-ene 1b. Compound 1a had been previously obtained by the
condensation of morpholine, nitromethane and diethyl ethoxy-
ethylidenemalonate in a yield of 40%,25 in turn the preparation
of diethyl ethoxyethylidenemalonate in a 66% yield represented
an additional stage.26 Herein, we obtained 2-morpholino-1-nitro-
alkenes 1a,b by the three-component condensation of
commercially available morpholine, nitromethane and the
corresponding ortho esters (Scheme 1) similarly to the described
preparation of 1-morpholino-2-nitroethylene.27 The yields of
compounds 1a and 1b were 67 and 76%, respectively.
Despite their poor accessibility, a-nitro ketones found an
application in the synthesis of relevant organic compounds.
O
MeNO2
R
RC(OEt)3
NO2
N
H
2-Morpholino-1-nitrobut-1-ene 1b represented
a
new
compound, its structure was confirmed by 1H NMR, 13C NMR,
IR spectroscopy, elemental analysis and X-ray data (Figure 1).†
O
N
O
i
ii
N
O
R
Na+
O
†
Crystal data for 1b. C8H14N2O3 (M = 186.21), space group P1,
1a,b
2a,b
a = 8.7836(6), b = 9.6570(6) and c = 11.6615(8) Å, a = 77.781(6),
b = 87.651(5) and g = 78.959(6)°, V = 948.86(11) Å3, Z = 4,
μ(MoKa) = 0.100 mm–1. At the angles 3.52° < 2q < 30.84°, total of
8842 reflections were measured, including 5137 unique reflections
(Rint = 0.0391) and 2117 reflections with I > 2s(I), which were used in all
calculations. The final R1 = 0.1492, wR2 = 0.2317 (all data) and R1 =
a R = Me, 67%
b R = Et, 76%
a R = Me, 70%
b R = Et, 96%
Scheme 1 Reagents and conditions: i, TsOH, 140 °C, 3 h; ii, NaOH, EtOH,
room temperature, 30 min.
© 2020 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
– 177 –

Mendeleev Commun., 2020, 30, 177–179
Cꢀꢁꢂ
Cꢀꢅꢂ
O(1)
N(3)
C(2)
N(11)
C(12)
Cꢀꢆꢂ
Cꢀꢇꢂ
Oꢀꢇꢂ
Cꢀꢈꢂ
Cꢀꢃꢂ
Nꢀꢄꢂ
C(1)
C(3)
C(4)
C(6)
Cꢀ2ꢂ
C(11)
C(10)
C(9)
C(5)
Oꢀ2ꢂ
Cꢀꢄꢂ
C(7)
N(2)
Nꢀ2ꢂ
O(3)
C(8)
Oꢀꢄꢂ
O(2)
Figure 1 Molecular structure of compound 1b drawn with 50% probability
displacement ellipsoids.
Figure 2 Molecular structure of compound 4b drawn with 50% probability
displacement ellipsoids.
O
Stirring 2-morpholino-1-nitroalk-1-enes 1a,b in alcoholic
solution of NaOH (or KOH) led to sodium (or potassium) salts
of nitroacetone and 1-nitrobutan-2-one in 70 and 96% yields,
respectively (see Scheme 1). They were isolated and characterized
O2N
R
i
+ PhN2+Cl–
2a,b
N
a R = Me, 69%
b R = Et, 73%
HN
Ph
1
by H NMR, 13C NMR and IR spectroscopy. When an aqueous
5a,b
alkali solution was used, hydrolysis of 2-morpholino-1-nitro-
alkenes also occurred, however the salts of nitro ketones did not
precipitate and could be used in further reactions in situ.
The synthesized salts of a-nitro ketones were found to be able
to enter triple condensation with aromatic aldehydes and urea.
The resulting substituted pyrimidines 4a–d were obtained in
yields of 81–89% (Scheme 2). The similar transformation was
reported for free a-nitro ketones.28
The physicochemical characteristics of the synthesized
products 4 correlate well with the known data. The structure of
new 6-ethyl-5-nitro-4-phenyl-3,4-dihydropyrimidinone 4b was
confirmed by X-ray analysis (Figure 2).†
Scheme 3 Reagents and conditions: i, AcONa, H2O, room temperature,
30 min.
The synthesized salts of nitro ketones can be used as well
for the preparation of a-nitro-a-phenylhydrazono ketones 5a,b
(Scheme 3) upon treatment with phenyldiazonium chloride.
The obtained compounds 5a,b were identical to those
described.29
In summary, a new safe and efficient synthesis of sodium or
potassium salts of a-nitro ketones has been developed. These
salts can be used in the reactions known for free unstable a-nitro
ketones. The results obtained can promote the intensive use of
nitro ketones for the synthesis of promising organic compounds.
Asanexample, duetothehighrateofhydrolysisof2-morpholino-
1-nitroalkenes, the freshly prepared solutions of a-nitro ketone
salts can be used in situ for azo coupling reactions, however, the
presence of morpholine as the hydrolysis product should be
taken into account.
O
O
HN
NH
i
2a,b + ArCHO +
3a,b
H2N
NH2
Ar
Ar
R
NO2
4a–d
3a Ar = 4-MeOC6H4
3b Ar = Ph
R
Yield (%)
This work was supported by the Russian Foundation for Basic
Research (grant no. 19-33-90086). The authors are grateful to
the Laboratory for Comprehensive Research and Expert
Evaluation of Organic Materials under the direction of
O. S. Eltsov for recording NMR and IR spectra.
Me
Et
Ph
Ph
86
87
4a
4b
4c
4d
Me 4-MeOC6H4 81
Et
4-MeOC6H4 89
Scheme 2 Reagents and conditions: i, HCl, EtOH, reflux, 7 h.
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2020.03.015.
= 0.0644, wR2 = 0.1666 [I > 2s(I)], GOOF = 1.002. Largest diff. peak/
hole 0.424 and –0.195 e Å–3.
Crystal data for 4b. C12H13N3O3 (M = 247.25), space group P21,
a = 7.2666(11), b = 29.257(3) and c = 11.8861(17) Å, b = 103.296(14)°,
V = 2459.3(6) Å3, Z = 8, μ(MoKa) = 0.098 mm–1. At the angles
3.56° < 2q < 28.28°, total of 16126 reflections were measured, uncluding
6170 unique reflections (Rint = 0.0549) and 3059 reflections with
I > 2s(I), which were used in all calculations. The final R1 = 0.1429,
wR2 = 0.2248 (all data) and R1 = 0.0699, wR2 = 0.1685 [I > 2s(I)],
GOOF = 1.005. Largest diff. peak/hole 0.275 and –0.239 e Å–3.
The XRD analysis was accomplished on an Xcalibur 3 diffractometer
using standard procedure [MoKa-irradiation, graphite monochromator,
l = 0.71073 Å, w-scans with 1° step, 295(2) K]. Using Olex2, the
structure was solved with a ShelXS structure solution program using
Direct Methods and refined using a ShelXL refinement package with the
Least Squares minimization in anisotropic approximation for
nonhydrogen atoms. The H-atoms were added in the calculated positions
and refined using the riding model in isotropic approximation.
CCDC 1948033 and 1948034 contain the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk.
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Received: 22nd August 2019; Com. 19/6016
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