Nitration of aryl cyclopropyl ketones using HNO2

Full text of DOI:10.1007/s10593-011-0768-2

Chemistry of Heterocyclic Compounds, Vol. 47, No. 3, June 2011 (Russian Original Vol. 47, No. 3,March, 2011)
NITRATION OF ARYL CYCLOPROPYL KETONES USING HNO2
R. A. Gazzaeva1*, A. N. Fedotov2, and S. S. Mochalov2
Keywords: cyclopropyl 4-methoxyphenyl ketone, cyclopropyl thienyl ketone, cyclopropyl phenyl ketone,
nitration.
Arylcyclopropanes containing electron-acceptor substituents in both the benzene and the small ring react
with in situ generated nitrous acid with the insertion of an N=O fragment into the three-carbon ring resulting in
the formation of substituted isoxazoles and isoxazolines [1-3]. We have proposed that aryl cyclopropyl ketones
containing an electron-donor type aryl fragment can also be converted to the corresponding heterocycles in the
presence of the indicated nitrosylating agent. However, it was found that the cyclopropane fragment of the
cyclopropyl 4-methoxyphenyl ketone (1) and cyclopropyl 2-thienyl ketone (2) is not opened by the action of a
nitrosyl cation under the conditions of generation of HNO2 whereas the aromatic ring of the ketones introduced
into the reaction undergoes an electrophilic nitration. The major part of the starting material is returned
unchanged. It was of interest that cyclopropyl phenyl ketone does not overall react with HNO2 in the conditions
indicated.
O
O
NaNO2, CF3COOH
CHCl3, -10 oC
MeO
O2N
MeO
1
NO2
S
3
NaNO2, CF3COOH
CHCl3, -10 oC
S
O
O
4
2
In principle, the electrophilic nitration of aromatic substrates in the presence of nitrous acid is an
established fact [4] but the formation of nitro-substituted acyl benzenes from aryl ketones using this reagent has
not been observed to this time. In this connection we have specifically shown that the conversion of aryl ketone
1 and hetaryl ketone 2 to the nitro-substituted compounds 3 and 4 is significantly increased if the conditions of
study [4] are used with a substrate to reagent ratio of 1:3.
_______
* To whom correspondence should be addressed, e-mail: gazzaeva@mail.ru.
1K. L. Khetagurov North Ossetian State University, 46 Vatutin St., Vladikavkaz 362000, Russia.
2M. V. Lomonosov Moskow State University, 1-3 Leninskiye Gory, Moscow 119991, Russia; e-mail:
ssmoch@org.chem.msu.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 459-461, March, 2011. Original
article submitted March 17, 2011.
0009-3122/11/4703-0379©2011 Springer Science+Business Media, Inc.
379

IR spectra were recorded on a UR-20 instrument using vaseline oil. 1H and 13C NMR spectra were taken
on a Varian VXR-400 spectrometer using CDCl3 with the residual CHCl3 in the deuterated solvent as internal
standard. Mass spectra were taken on a Finnigan SSQ 7000 GC-MS type instrument using a capillary column
(30 m×2 mm, DB-1 stationary phase) with helium gas carrier (40 ml/min), temperature program from 50 to
300ºC (10 deg/min), and ionization energy 70 eV. Separation of the reaction mixtures and monitoring of the
purity of the reaction products was carried out on columns or Silufol plates and on Al2O3 (Brockmann activity
II) with diethyl ether and petroleum ether (40-70ºC) as eluent (1:2 by volume).
Nitration of Aryl Cyclopropyl Ketones 1 and 2 Using HNO2 (General Method). NaNO2 (10 mmol)
was added over 30 min to a solution of compound 1 or 2 (10 mmol) in CF3COOH (5 ml) and CHCl3 (10 ml) at -
10ºC. After the addition of the sodium nitrite the reaction mixture was held at this temperature for 30 min,
poured into water, and extracted with chloroform. The extract was dried over MgSO4, solvent was evaporated,
and the residue was chromatographed on silica gel.
Compounds 3 and 4 were prepared by this method.
4-Cyclopropylcarbonyl-2-nitroanisole (3) was synthesized from the cyclopropyl 4-methoxyphenyl
ketone (1). Yield 82% (based on the starting material undergoing the reaction); mp 76-77ºC (hexane). IR
spectrum, , cm-1: 1670 (C=O); 1550, 1335 (NO2). 1H NMR spectrum, , ppm (J, Hz): 1.06 (2H, m, CH2); 1.22
3
3
(2H, m, CH2); 2.59 (1H, m, CH); 4.02 (3H, s, OCH3); 7.15 (1H, d, J = 8.8, H arom.); 8.19 (1H, dd, J = 8.8,
4J = 2.0, H arom.); 8.49 (1H, d, J = 2.0, H arom.). 13C NMR spectrum, , ppm: 12.02; 16.91; 56.90; 113.27;
4
125.91; 130.31; 133.80; 139.21; 156.01; 197.30. Mass spectrum, m/z (Irel, %): 221 [M]+ (24), 180 (100), 133
(7), 76 (15), 41 (6). Found, %: C 59.67; H 5.08; N 6.11. C11H11NO4. Calculated, %: C 59.73; H 5.01; N 6.33.
5-Cyclopropylcarbonyl-2-nitrothiophene (4) was prepared from the cyclopropyl 2-thienyl ketone (2).
Yield 93% (based on the starting material undergoing the reaction); mp 104-105ºC (hexane). IR spectrum, ,
cm-1: 1680 (C=O); 1540, 1340 (NO2). H NMR spectrum, , ppm (J, Hz): 1.06 (2H, m, CH2); 1.26 (2H, m,
1
CH2); 2.55 (1H, m, CH); 7.68 (1H, d, J = 4.3, H thiophene); 7.90 (1H, d, J = 4.3, H thiophene). 13C NMR
spectrum, , ppm: 12.77; 18.16; 128.43; 129.26; 148.74; 156.05; 192.86. Mass spectrum, m/z (Irel, %): 197 [M]+
(19), 156 (100), 110 (24), 98 (8), 82 (12), 69 (24), 41 (15). Found, %: C 48.62; H 3.28; N 6.81. C8H7NO3S.
Calculated, %: C 48.72; H 3.58; N 7.10.
3
3
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