New stable form of nitroacetonitrile

Article abstract of DOI:10.1016/j.mencom.2016.03.031

Oxidation of ethyl cyanoglyoxylate 2-oxime followed by KOH treatment affords stable potassium salt of nitroacetonitrile which is a reliable substitute of hazardous free nitroacetonitrile in organic synthesis.

Full text of DOI:10.1016/j.mencom.2016.03.031

Mendeleev
Communications
Mendeleev Commun., 2016, 26, 172–173
New stable form of nitroacetonitrile
Egor K. Voinkov,*a Evgeny N. Ulomskiy,a,b Vladimir L. Rusinov,a,b Konstantin V. Savateev,a
Victor V. Fedotov,a Evgeny B. Gorbunov,a,b Maksim L. Isenovb and Oleg S. Eltsova
a Department of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Ekaterinburg,
Russian Federation. E-mail: voinkov-egor@mail.ru
b I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
620990 Ekaterinburg, Russian Federation
DOI: 10.1016/j.mencom.2016.03.031
Oxidation of ethyl cyanoglyoxylate 2-oxime followed by
KOH treatment affords stable potassium salt of nitroaceto-
nitrile which is a reliable substitute of hazardous free nitro-
acetonitrile in organic synthesis.
KMnO4,
KOH
NC
CO2Et
NOH
NO2
CN
RCHO
H+
NC CH NO2 K+
R
Reactivity of nitroacetonitrile (NAN) is poorly studied due to its
very low thermodynamic stability.1 Most of the reports is limited
to azo coupling,2 Knoevenagel condensation3–7 and similar pro-
cesses.8–10 At the same time, possibilities of using NAN in the
synthesis of 3-amino-4-nitropyrazoles,11 chromenes,12 azolo-
[5,1-c][1,2,4]triazines, 6-azauracils14,15 and 2,4,6-tricyano-
pyridine-N-oxide16 are documented. This brings a challenge to
create a stable form of NAN, which can open new possibilities of
its application. One of successful approaches is the decomposi-
tion of pyridinium salt of nitroisoxazolone.1,17,18
Herein, we propose an easy method of obtaining stable potas-
sium salt of NAN from more available reactants (cf. refs. 1,17,18)
and its subjecting to some reactions reported earlier for free NAN.
Previously, cesium,19 arylammonium and ammonium salts20 were
prepared directly from NAN. Obviously, these methods suffer
explosion hazards when preparing NAN from methazonic acid.
In this work, ethyl nitrocyanoacetate potassium salt 1 was
used as the starting compound for the synthesis of potassium
salt of NAN 2 (Scheme 1). Oxidation of ethyl cyanoglyoxylate
2-oxime 3 at 35–40°C gives compound 1 in 63–67% yield.
According to the reaction equation it is necessary to add 1/3 equiv.
of alkali to fully transfer compound 3 into aqueous phase.
dipotassium salt of nitrocyanoacetic acid which is then readily
converted into the final NAN salt 2 in 45% yield. This salt is
stable under normal conditions for a long time.†
The structure of compound 2 was proved on the basis of IR,
1H, 13C NMR and 2D HMBC 1H-15N NMR spectra and elemental
analysis. The ultimate confirmation was established by a single
crystal X-ray analysis (Figure 1).‡
†
Ethyl nitrocyanoacetate potassium salt 1. A solution of KMnO4 (23.7 g,
0.15 mol) in water (400 ml) was prepared. The solution of KOH (1.848 g,
0.033 mol) in water (35 ml) was added to ethyl cyanoglyoxylate-2-oxime
3 (14.2 g, 0.1 mol) in warm water (240 ml). The solution of KMnO4 was
added dropwise to compound 3 for 30 min maintaining the temperature
not higher than 40°C. The mixture was stirred at room temperature until
the permanganate was consumed (a sample on the filter paper does not
give purple color). The precipitate was filtered off, the filtrate was con-
centrated on a rotary evaporator at T < 40°C, the dry residue was washed
with ethanol and filtered. The precipitate was recrystallized from ethanol
1
and dried. Yield 12.4 g (63%), white crystals, mp 245°C. H NMR, d:
1.22 (t, 3H, Me, J 7.10 Hz), 4.05 (q, 2H, CH2, J 7.10 Hz). IR (n/cm–1):
772, 1015, 1089, 1222, 1292, 1337, 1367, 1700, 2211. Found (%): C, 30.41,
H, 2.76, N, 14.17. Calc. for C5H5N2O4K (%): C, 30.61, H, 2.57, N, 14.28.
Nitroacetonitrile potassium salt 2. Salt 1 (9.8 g, 0.05 mol) was added
to a solution of KOH (2.8 g, 0.05 mol) in water (40 ml) and the mixture
was stirred overnight. Next day the pH of the solution was reduced from
14 to 9. The solvent was removed in vacuo at T < 40°C, the dry residue
was washed with ethanol, filtered and dried in air. This material was
extracted with methanol (3×50 ml) at room temperature and then 50 ml on
refluxing. The methanol extract was concentrated on a rotary evaporator
at T < 30°C, the residue was washed with ethanol and filtered. Yield 2.8 g
O
O
NC
NC
2/3 KMnO4 + 1/3 KOH
– 2/3 MnO2, – 2/3 H2O
OEt
NC
OEt
NO2 K+
NOH
3
1
1
O
(45%), pale-yellow crystals, mp 137°C. H NMR (DMSO-d6) d: 5.62
NC
H
H2O
(s, 1H, CH). 1H NMR (D2O) d: 4.68 (s, 1H, CH). 13C NMR (GATE) d:
81.10 (d, CH, J 197.30 Hz), 119.68 (d, CN, J 9.00 Hz). 15N NMR, d:
267.4 (CN), 367.7 (NO2). IR (n/cm–1): 973, 1240, 1339, 1454, 1631,
1695, 2198, 3083, 3436. Found (%): C, 19.23, H, 0.49, N, 22.17. Calc. for
C2HN2O2K (%): C, 19.35, H, 0.81, N, 22.57.
KOH
O–K+
– KHCO3
NO2 K+
NO2 K+
2
Scheme 1
‡
Crystal data for 2. The fragment of crystal (colorless rhombus,
0.25×0.20×0.15 mm) of compound 2 (C2HO2N2K, M = 124.14) was used
for X-ray analysis. Analysis was performed at 295(2) K on an Xcalibur 3
diffractometer by standard procedure (graphite monochromated, MoKa
radiation, w-scanning). Space group Fdd2, a = 14.447(3), b = 11.1109(4)
and c = 12.003(3) Å, V = 1926.8(7) Å3, Z = 16. 6208 reflections were
measured, 2.87 < q < 33.57°, among them 956 unique (Rint = 0.0343),
741 reflections with I > 2s(I). The structure was solved and refined using
Salt 1 is a stable available easy-to-handle compound conve-
nient for further preparation of potassium salt of NAN 2 (see
Scheme 1). We have found that when stirring compound 1 in the
equivalent of 5–10% KOH solution at room temperature, the pH
of the solution decreases to 9 within several hours. Apparently,
the process starts with the ester hydrolysis to form the unstable
© 2016 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2016, 26, 172–173
shown that this salt can be a promising substitute for the free
nitroacetonitrile in a variety of organic reactions.
N(1)
C(2)
C(1)
O(1)
H(1)
C(1)
O(2)
N(2)
O(2)
The work was supported by the Russian Science Foundation
(grant no. 14-13-01301).
C(2)
K(1)
N(1)
N(2)
H(1)
K(1)
O(1)
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2016.03.031.
Figure 1 Molecular structure of nitroacetonitrile potassium salt 2. Bond
lengths (Å) and angles (°): N(1)–C(2) 1.142, C(2)–C(1) 1.388, C(1)–H(1)
0.995, C(1)–N(2) 1.323, N(2)–O(1) 1.273, N(2)–O(2) 1.266, O(1)–K(1)
2.903, O(2)–K(2) 2.797; N(1)–C(2)–C(1) 178.27, C(2)–C(1)–N(2) 117.75,
C(2)–C(1)–H(1) 123.82, C(1)–N(2)–O(2) 120.83, O(2)–N(2)–O(1) 118.26.
References
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Nitroacetonitrile potassium salt 2 as the very NAN readily
reacts with aromatic and heterocyclic aldehydes 4a–e to form
3-(het)aryl-2-nitroacrylonitriles 5 (Scheme 2).§
NO2
2
H+
R
R
O
CN
5a–e
4a–e
a R = Ph
d R = 2-furyl
b R = 4-Me2NC6H4
c R = 4-MeOC6H4
e R = 2-thienyl
8 O. S. Wolfbeis, Ber., 1981, 114, 3471.
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Scheme 2
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Aleksandrov, Chem. Heterocycl. Compd. (Engl. Transl.), 1985, 21, 576
(Khim. Geterotsikl. Soedin., 1985, 21, 682).
Salt 2 turned out to be a suitable water-soluble azo coupling
reagent. In this way, 2-nitro-2-phenylhydrazonoacetonitrile 6 was
obtained by reacting phenyldiazonium salt with the potassium
salt of NAN instead of NAN2 (Scheme 3).
CN
NaNO2
HCl
2
H
PhNH2
PhN2 Cl–
N
NaOAc
Ph
N
NO2
6
15 V. L. Rusinov, T. V. Dragunova, V. A. Zyryanov, G. G. Aleksandrov,
N. A. Klyuev and O. N. Chupakhin, Chem. Heterocycl. Compd. (Engl.
Transl.), 1984, 20, 455 (Khim. Geterotsikl. Soedin., 1984, 20, 557).
16 K.-D. Gundermann and H.-U. Alles, Angew. Chem., 1966, 78, 906.
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19 H. Brand, J. F. Liebman, A. Schulz, P. Mayer and A. Villinger, Eur. J.
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Scheme 3
The procedure can be simplified if one does not isolate salt 2
from the reaction mixture after hydrolysis of ester 1. For this
purpose the required amount of sodium acetate solution is added
to the crude mixture containing salt 2. The resulting solution is
used directly for the azo coupling.¶
In summary, we have developed a new safe and easy method
for the synthesis of the potassium salt of nitroacetonitrile, and
the SHELX97 program package. All non-hydrogen atoms were refined
anisotropically, the positions of the hydrogen atoms were calculated as a
riding model in isotropic approximation. The correction of the absorption
was taken into account using MultiScan technique (m = 0.978 mm–1).
Goodness of fit at F2 is 1.003; final R values [I > 2s(I)], R1 = 0.0236, wR2 =
= 0.0487; R values (all reflections), R1 = 0.0331, wR2 = 0.0496. Residual
electronic density emax/emin was 0.169/–0.223 eÅ–3.
Received: 5th October 2015; Com. 15/4743
¶
CCDC 1453318 contains 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.
Nitro(phenylhydrazono)acetonitrile 6. Salt 1 (0.353 g, 0.0018 mol) was
added to a solution of KOH (0.1 g, 0.0018 mol) in water (5 ml) and the
mixture was stirred overnight. Next day the pH of the solution was reduced
from 14 to 9 and aqueous AcONa solution (1.4 ml, 3.9 m, 0.0054 mol) was
added and the mixture was cooled to 5°C. In another vessel, cold solution of
sodium nitrite (0.138 g, 0.002 mol) in water (3 ml) was added to a solution
of aniline (0.167 g, 0.0018 mol) in water (3 ml) and 12 m HCl (0.45 ml,
0.0054 mol) at –5°C maintaining the temperature of the reaction mixture not
higher than 0°C. This mixture was stirred for 10 min and transferred to the
above cooled solution of nitroacetonitrile with sodium acetate. The resulting
suspension was stirred at room temperature for 1 h, filtered, washed with an
aqueous alcohol solution and dried in air. Yield 0.14 g (41%), orange powder,
mp 152°C (lit.,21 146°C). 1H NMR, d: 7.15–7.79 (m, 5H, 5CH), 13.38 (br.s,
1H, NH). IR (n/cm–1): 686, 731, 747, 761, 828, 890, 1150, 1231, 1247, 1318,
1412, 1487, 1532, 2232, 3191. Found (%): C, 50.33; H, 3.39; N, 29.07. Calc.
for C8H6N4O2 (%): C, 50.53; H, 3.18; N, 29.46.
§
2-Nitro-3-phenylacrylonitrile 5a. Ethanol (1 ml), nitroacetonitrile potas-
sium salt 2 (0.248 g, 0.002 mol) and benzaldehyde 4a (0.212 g, 0.002 mol)
were added sequentially to trifluoracetic acid (0.456 g, 0.004 mol) on
stirring. The mixture was stirred for 3 h at room temperature and evaporated
to dryness. Product 5a was extracted with boiling CCl4 and crystallized
under cooling in ice bath. The precipitate was filtered, washed with CCl4
and dried. Yield 0.216 g (62%), yellow crystals, mp 101°C (lit.,4 101°C).
1H NMR, d: 7.60–7.74 (m, 3H, 3CH), 8.11 (m, 2H, 2CH), 9.01 (s, 1H, CH).
IR (n/cm–1): 1183, 1210, 1294, 1320, 1537, 1587, 1615, 2229, 3044. Found
(%): C, 61.85; H, 3.46; N, 16.04. Calc. for C9H6N2O2 (%): C, 62.07; H, 3.47;
N, 16.08.
For synthesis and characteristics of compounds 5b–e, see Online
Supplementary Materials.
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